Lambda Light Chain Deposition Research Articles

Spatial resolution of renal amyloid deposits through MALDI-MSI: a combined digital and molecular approach to monoclonal gammopathies

AimsIdentification and characterisation of monoclonal gammopathies of renal significance (MGRS) is critical for therapeutic purposes. Amyloidosis represents one of the most common forms of MGRS, and renal biopsy remains the...

Multiple Myeloma Presenting as Acute Kidney Failure Secondary to Lambda Light Chain Deposition

Renal monoclonal immunoglobulin deposition disease (MIDD) is a rare disease defined by deposition of monoclonal light chains and/or heavy chains on basement membranes and vascular walls of the kidney. We describe a case of a 71-year-old woman with kidney failure secondary to monoclonal immunoglobulin deposition disease lambda in association with plasma cell dyscrasia. Her initial serum protein electrophoresis did not demonstrate a monoclonal protein, and classic cast nephropathy was absent on renal biopsy. However, lambda light chain deposits and associated changes confirmed MIDD. She achieved a very good partial response (VGRP) after 8 cycles of CyBorD (cyclophosphamide, bortezomib, dexamethasone) and her kidney function improved. This case highlights the importance of an early diagnostic with renal biopsy to prevent end-stage renal disease. A review of the existing literature and a discussion on the management of the disease is presented.

Clinicopathologic Significance of Predominant Lambda Light Chain Deposition in IgA Nephropathy

IgA nephropathy (IgAN) differs from other glomerular diseases by the frequently predominant lambda over kappa light chain deposition. Using the Cure Glomerulonephropathy (CureGN) IgAN cohort, we aimed to determine whether predominant lambda chain deposition is associated with worse clinical outcomes or histopathologic markers of more active disease. Patients were categorized based on the intensity of light chain staining. The lambda dominant (LD) group was defined by a difference in intensity score of lambda minus kappa≥ 1+ and the kappa-lambda codominant (KL) group by a difference< 1+. We compared the clinical course of patients in each category from the time of kidney biopsy and time of enrollment into CureGN to the time of remission (proteinuria< 0.3 g/g), 50% reduction in estimated glomerular filtration rate (eGFR), or progression to end-stage kidney disease (ESKD). We also analyzed differences in histopathologic characteristics between the 2 groups. Among 440 patients, we found no significant differences between groups in baseline clinical characteristics nor in rates of remission, 50% reduction in eGFR, or progression to ESKD. Patients in the LD group had a modestly greater frequency of IgG staining≥ 1+. The biopsy results of 234 patients reviewed by CureGN pathologists revealed a greater frequency of endocapillary hypercellularity (51.1% vs. 36.3%, P= 0.04) in the LD group, but no other significant difference in histopathologic features. In IgAN, we found an association between lambda predominance and increased endocapillary hypercellularity, but no association with clinical outcomes.

The clinicopathological characteristics and outcomes of IgA nephropathy with predominant lambda or kappa light-chain deposition.

IgA nephropathy (IgAN) patients with monoclonal light-chain deposition may be at potential risk of hematological progression. However, whether the clinical characteristics of the patients with predominant lambda or kappa light-chain deposition were consistent with monoclonal light-chain deposition is limited to anecdotes. We retrospectively studied patients in whom immunofluorescence showed IgA-alone deposits (n = 617) between January 2016 and January 2020. We divided the patients into two groups, the predominant lambda or kappa light-chain deposition group and the control group. Predominant lambda or kappa light-chain deposition was defined as the deposition intensity of kappa or lambda being +- and the other deposition intensity being ≥ 2 + . Nineteen patients had predominant lambda or kappa light-chain deposition. The patients had a median age of 32years. The median proteinuria was 0.9g/day. The median eGFR was 79.8ml/min per 1.73m2. Two patients had a mildly abnormal FLC ratio, but serum immunofixation electrophoresis showed polyclonal immunoglobulin. Eighteen patients showed lambda light chain-dominated deposition. In electron microscopy, organized structures in dense deposits were not observed in all patients. Nine patients with proteinuria ≥ 1.0g/day received corticosteroids and immunosuppressants. The median follow-up time was 21months. The rate of proteinuria remission was 50%. The clinical and pathological characteristics and outcomes were not significantly different between the predominant lambda or kappa light-chain deposition group and the control group. The result for IgAN patients with predominant kappa/lambda light-chain deposition seemed to be the same as that of IgAN patients with light-chain codeposition. However, as this was a single-center study with a small size, further multicenter studies and long-term follow-up are needed to confirm our findings.

Gastric Plasmacytoma with Immunoglobulin Lambda Light Chain Deposition in a Dog

A 12-year-old castrated male Jack Russell Terrier presented with intermittent vomiting. Abdominal ultrasonographic examination detected a thickened stomach wall with a mass measuring approximately 1.5cm in diameter. Computed tomography revealed a solitary mass measuring approximately 2.1cm in diameter between the submucosa and muscle layers in the greater curvature the pyloric region of the stomach, and a swelling in the hepatic lymph node. The gastric mass was composed of round neoplastic cells arranged in a diffuse pattern. The neoplastic cells had a round nucleus and a pale abundant cytoplasm. Multinucleated giant cells were often found. Hyalinized eosinophilic material, which did not stain with Congo red and had no affinity for thioflavin T, was also observed. Neoplastic cells were immunopositive for MUM1, CD79a and Ig lambda light chain but negative for CD3, CD20, BLA36, IgG and Ig kappa light chain. Stromal eosinophilic material was positive for Ig lambda light chain. The neoplasm was therefore diagnosed as a gastric plasmacytoma with non-amyloid Ig lambda light chain deposition.

Kappa light chain myeloma: A case report

Light chain myeloma nephropathy is the most common form of renal involvement in plasma cell dyscrasias. It usually causes tubulointerstitial renal damage. About one in five people with multiple myeloma produce only light chains. We report a case of lambda light chain deposition disease in a 61-year-old female who presented with acute renal failure . She is currently in partial remission following treatment with bortezomib, cyclophosphamide, and steroids.We present a case with rare kappa light chain myeloma with light chain deposition in renal tubules.

THE RARE ENTITY OF PULMONARY AMYLOIDOSIS

SESSION TITLE: Diffuse Lung Disease 2 SESSION TYPE: Fellow Case Reports PRESENTED ON: 10/07/2018 04:45 pm - 05:45 pm INTRODUCTION: Pulmonary amyloidosis is an uncommon disease, characterized by extracellular deposition of fibrillary protein in the lungs. It appears in three forms: tracheobronchial, nodular pulmonary, and alveolar septal. We report a rare case of single, nodular pulmonary amyloidosis in a middle aged Hispanic patient. CASE PRESENTATION: A 43 year old Hispanic female, never smoker, was referred to our Chest clinic by her gastroenterologist, when an abdominal imaging for possible gallstones revealed a 2.1cm speculated right middle lobe nodule. A dedicated chest Ct then confirmed the nodule but also revealed several thin walled lung cysts of various sizes. She denied any pulmonary or constitutional symptoms other than occasional dry cough. Her Pulmonary function test was normal. Patient then underwent CT guided biopsy of the lesion for concern of malignancy. Histopathologic examination of the biopsy specimen revealed it to be nodular parenchymal amyloidosis of localized AL type. Full work up for amyloidosis then revealed possible renal involvement. Patient currently being followed up by nephrology and us for further management DISCUSSION: Amyloidosis is characterized by extra-cellular deposits of an insoluble fibrillar protein (amyloid) with a corrugated plate structure. Upon reacting with Congo red, the protein exhibits an apple-green birefringence under a polarized microscope. The mean age of onset is 55-60 years. Cases with kappa and lambda light chain deposits are referred to as amyloid light chain (AL) amyloidosis, and those with plasma amyloid P deposits due to chronic infectious disease are called amyloid A (AA) amyloidosis. Amyloidosis localized to the respiratory system is very rare, and is classified as parenchymal nodular, tracheobronchial, or diffuse alveolar septal according to the type of pulmonary invasion involved. Cysts are extremely rare. The tracheobronchial type can accompany a variety of symptoms, including dyspnea, hemoptysis, and cough, but it can also be asymptomatic in .Pulmonary parenchymal nodular type is mostly asymptomatic. The diffuse alveolar septal type exhibits progressive pulmonary fibrosis patterns, and most patients experience respiratory failure leading to death. Management of localized pulmonary amyloidosis is dependent on the severity of symptoms, systemic or localised and the type of amyloid protein. Asymptomatic patients may not require treatment. CONCLUSIONS: A single nodular lesion can mimic various conditions, including malignancy, pulmonary tuberculosis, and fungal infection. Once single nodular lesions are observed, it is necessary to have a broad differential diagnosis including amyloidosis.Our case is unique in its rarity and atypical presentation of pulmonary amyloid and also its occurrence in a younger population than described in literature. Reference #1: Lee SH, Ko YC, Jeong JP, et al. Single Nodular Pulmonary Amyloidosis: Case Report. Tuberculosis and Respiratory Diseases. 2015;78(4):385-389. https://doi.org/10.4046/trd.2015.78.4.385. Reference #2: Andras Khoor and Thomas V. Colby (2017) Amyloidosis of the Lung. Archives of Pathology & Laboratory Medicine: February 2017, Vol. 141, No. 2, pp. 247-254. DISCLOSURES: No relevant relationships by Prarthna Chandar, source=Web Response No relevant relationships by Sakthidev Kulandaisamy, source=Web Response No relevant relationships by Ben Shamian, source=Web Response No relevant relationships by Shyam Shankar, source=Web Response no disclosure on file for Jack Twersky

Cutis laxa associated with monoclonal gammopathy: 14 new cases and review of the literature

Cutis laxa associated with monoclonal gammopathy: 14 new cases and review of the literature

A Case of Abdominal Aortic Retroperitoneal and Mesenteric Amyloid Light Chain Amyloidoma.

We report the case of a Japanese woman with amyloid light chain (AL) amyloidoma in the abdominal aortic retroperitoneum and mesentery. Irregular soft tissue mass lesions with calcification in the abdominal aortic retroperitoneum and mesentery were initially detected by computed tomography at another hospital. The lesions gradually compressed the duodenum, causing symptoms of bowel obstruction. The patient was clinically diagnosed with retroperitoneal fibrosis, and prednisolone was administered at a dose of 40 mg/day. However, the lesions did not change in size and her symptoms continued. She was transferred to our hospital and underwent mesenteric biopsy for histopathology using abdominal laparotomy. The histopathological and immunohistological findings of the mesenteric specimen demonstrated lambda light chain deposition. Accordingly, the patient was finally diagnosed with AL amyloidoma with no evidence of systemic amyloidosis. After laparotomy, her general condition worsened because of complications of pneumonia and deep vein thrombosis. She died suddenly from acute myocardial infarction. We have concluded that abdominal aortic retroperitoneal and mesenteric AL amyloidoma may have very poor prognoses in accordance with previous reports. In addition, the size and location of AL amyloidoma directly influence the prognosis. We suggest that early histopathology is important for improving prognosis.

Nephrotic syndrome secondary to proliferative glomerulonephritis with monoclonal immunoglobulin deposits of lambda light chain.

We describe a rare case of a 46-year-old woman with history of refractory nephrotic syndrome and hypertension who presented with worsening proteinuria and kidney function. Work-up for both autoimmune and infectious diseases and hematologic malignancies including multiple myeloma were negative. Kidney biopsy demonstrated glomerular sclerotic change with lambda light chain deposits in the subendothelial space, which is consistent with proliferative glomerulonephritis with monoclonal immunoglobulin deposit (PGNMID). The patient was treated with bortezomib and dexamethasone without clinical improvement and eventually became hemodialysis dependent.

Histopathology of chronic kidney disease of unknown etiology in Salvadoran agricultural communities.

For at least a decade, a chronic kidney disease unassociated with diabetes mellitus, hypertension or any of the more common traditional causes, has been reported in Salvadoran agricultural communities. Characterize histopathology of chronic kidney disease of unknown etiology in patients from Salvadoran agricultural communities, describe renal damage associated with each disease stage, and assess associations between histopathological alterations and sociodemographic variables. The study involved 46 patients of both sexes, aged =18 years. After clinical, laboratory and imaging examinations, kidney biopsies were performed and renal tissue assessed for interstitial fibrosis, tubular atrophy, interstitial inflammatory infiltration, sclerosis, increase in glomerular size and extraglomerular vascular lesions (according to the Banff 97 classification used for kidney transplant rejection). Special staining was done: Schiff periodic acid, Masson trichrome and methenamine silver. Immunofluorescence techniques were used to evaluate IgA, IgG, IgM, complement C1q and C3, fibrin, and kappa and lambda light chain deposits. The main findings were interstitial fibrosis and tubular atrophy with or without inflammatory monocyte infiltration. In addition, generalized sclerosis, increased glomerular size, collapse of some glomerular tufts, and lesions of extraglomerular blood vessels (such as intimal proliferation and thickening and vacuolization of the tunica media) were observed. Interstitial fibrosis and glomerulosclerosis were associated with male sex. Sugarcane workers showed more interstitial fibrosis and tubular atrophy and less glomerulomegaly than other occupational groups. The morphological pattern in all biopsies was one of chronic tubulointerstitial nephropathy with secondary glomerular and vascular damage, in different stages of evolution of chronic kidney disease, independent of age, sex or occupation.

Cutis laxa adquirido asociado a gammapatía monoclonal y enfermedad por depósito de cadenas ligeras lambda

Author(s): Gonzalez-Rodriguez, Antonio J; Bella-Navarro, Rebeca; Ramon Quiles, Dolores; Jorda-Cuevas, Esperanza | Abstract: Cutis laxa is a rare entity characterized clinically by redundant skin that gives an appearance of premature aging. The appearance relates to a loss of elasticity because of the destruction of elastic fibers that affects the skin and other organs. It may be associated with inflammatory conditions or diseases, such as plasma cell dyscrasias. We report the case of a 54-year-old man with acquired cutis laxa, which preceded the development of IgG-lambda monoclonal gammopathy with lambda light chain deposits in the kidney. The patient had a fatal outcome owing to severe and rapidly progressive renal failure. We emphasize the importance of recognizing a plasma cell dyscrasia in a patient with cutis laxa, although this association is rare.

Periventricular white matter immunoglobulin lambda light chain deposition disease diagnosed by proteomic analysis

Periventricular white matter immunoglobulin lambda light chain deposition disease diagnosed by proteomic analysis

Fibrillary inclusions in light chain proximal tubulopathy associated with myeloma.

A 66-year-old retired librarian was referred to the nephrology clinic for evaluation of a recent onset of asymptomatic proteinuria identified at a routine hypertension check-up. She had a 15-year history of hypertension and was treated with ramipril and bendrofluomethazide with no history of diabetes. The urinary protein–creatinine ratio was elevated at 819 mg/mmol, with no evidence of glycosuria, hypoalbuminaemia, acidaemia or impaired renal function (serum creatinine 78 μmol/L). Serum electrophoresis identified a monoclonal IgG kappa band quantified at 20 g/L with associated immunoparesis. Urinary immunofixation demonstrated kappa free light chains. On renal biopsy (Figure 1), there was marked vacuolation of tubular epithelial cells and electron microscopy demonstrated filaments 6 nm in diameter in these cells (Figures 2 and ​and3).3). Congo red staining for amyloid was negative. Immunoflorescence for light chains was negative on frozen sections but protease-digested paraffin sections showed kappa but not lambda light chain deposition in tubular epithelial cells. These findings are consistent with a proximal tubulopathy with fibrillary inclusions related to a kappa light chain plasma cell dyscrasia. Fig. 1. Light microscopy demonstrating vacuolation of tubular epithelial cells. Fig. 2. Electron micrograph of a tubular epithelial cell showing numerous vacuoles in the cytoplasm. Fig. 3. Higher power view of cytoplasmic vacuole showing numerous closely packed filaments 6 nm in diameter. Subsequent bone marrow was hypercellular with 61% plasma cells, which were kappa light chain restricted; she was started on a CTD (cyclophosphamide, thalidomide and dexamethasone) chemotherapeutic regime and has preserved her renal function but has continuing proteinuria. Light chain proximal tubulopathy is an increasingly recognized though still uncommon renal complication of myeloma almost exclusively related to light chain kappa [1]. Some individuals may manifest an associated Fanconi syndrome that was not seen in this woman. Diagnosis can be difficult with frequently non-specific light microscopy findings; on ultrastructural examination, crystalloid inclusions are frequently seen but occasionally may be fibrillary in nature [2]. Crystalloid deposition is thought to occur due to a resistance of the light chain-variable region to lysosymal proteolysis in the proximal tubule [3]. The unusual fibrillary appearances seen here may relate to the physicochemical properties determined by the amino acid sequence in the variable region.

Complete remission of lambda light chain myeloma presenting with acute renal failure following treatment with bortezomib and steroids

About one in five people with multiple myeloma produce only light chains. Patients with lambda light chain disease have a three times worse prognosis than kappa light chain disease. We report a case of lambda light chain deposition disease in a 35-year-old female who presented with acute renal failure requiring hemodialysis. She had complete recovery and is now in complete remission following treatment with bortezomib and steroids.

Ligneous conjunctivitis in a patient with Crohn&amp;prime;s disease

Report the case of a patient with Crohn's disease and ligneous conjunctivitis. Interventional case report of a 27-year old female patient, with a 4-year history of Crohn's disease, was seen for right eye conjunctival ulcer after resolved chemical trauma. Conjunctival biopsy was performed for histopathology, immunofluorescence microscopy, and immunohistochemistry testing. Microbiology tests were negative for bacteria and fungi. PCR was negative for atypical mycobacteria and Herpes. Ocular Crohn's disease, Whipple disease, and amyloidosis were ruled out. Immunofluorescence microscopy revealed characteristic IgG kappa and lambda light chain deposits, and fibrin deposition was confirmed through Lendrum's Martius, Scarlet, and Blue technique. Endogenous plasminogen levels were normal. Recurrent ulcers did not resolve after treatment with infliximab, but only after four surgeries, topical steroids, 1% cyclosporine, heparin (5000 units/ml), and hyaluronidase (1.5 mg/ml). After 9 months of follow-up, nasal symblepharon was observed as sequela. We report the case of a patient with unilateral ligneous conjunctivitis, triggered by chemical injury, and Crohn's disease.

A 19‐year‐old Male with Generalized Seizures, Unconsciousness and a Deviation of Gaze

Light chain deposition disease (LCDD) is a form of monoclonal immunoglobulin deposition diseases (MIDD) which in contrast to light-chain derived (AL) amyloidosis is characterized by non-congophilic, non-fibrillary monoclonal protein deposits. Systemic organ deposits are common with the kidney being a major target organ. A clonal lymphoplasmocytic proliferation, e.g. plasmacytoma, is present in the majority of cases. Here we report on a 19-year-old male who presented with generalized seizures and an enhancing white matter lesion on MRI scans. A stereotactic brain biopsy revealed a low-grade B cell lymphoma with plasmacellular differentiation as well as lambda light chain deposits without birefringence under polarized microscopy. No systemic lymphoma manifestations or systemic light chain deposits were found, nor was a monoclonal gammopathy detectable in serum and urine. After systemic chemotherapy with three courses high-dose methotrexate the size of the lesion and the condition of the patient have remained stable for 24 months now. This is the first description of cerebral LCDD developing without systemic disease in conjunction with the diagnosis of a cerebral low-grade B cell lymphoma. We present the clinical, laboratory and radiological findings and discuss the pathogenesis of this unusual LCDD manifestation.

Lambda Light Chain Deposition Disease in a Renal Allograft

Light chain deposition disease (LCDD) of the kidney is characterized by deposition of monoclonal light chains predominantly in glomeruli and in tubular basement membranes. The disease is frequently associated with a lymphoproliferative disorder, and the majority of cases are caused by deposition of kappa light chains. Although the occurrence of de novo multiple myeloma after renal transplantation is uncommon, there are several reports of LCDD involving renal allografts, either de novo or in patients with a diagnosis of LCDD prior to transplantation. To the best of our knowledge, all previously described cases in allografts have been in patients with kappa chain deposition. The relative importance of intrinsic properties of the kidney in predisposing to either kappa or lambda light chain deposition is not known. We present a case of LCDD caused by deposition of lambda light chains in a patient who received a cadaveric renal transplant.

Congestive heart failure: revealing light chain deposition disease

We report a case of light chain deposition disease associated with multiple myeloma revealed by congestive heart failure. Endomyocardial biopsy showed Congo red negative deposits and lambda light chain deposits by the immunofluorescence method. After chemotherapy with melphalan and prednisone, complete remission of multiple myeloma and major improvement in cardiac condition were observed.

Complete Primary Sequences of Two λ Immunoglobulin Light Chains in Myelomas with Nonamyloid (Randall-Type) Light Chain Deposition Disease

We herein report on the first two primary sequences (BOU and RAC) of monoclonal light chains of the lambda type responsible for nonamyloid lambda light chain deposition disease. Both patients were affected with severe forms of myeloma complicated with renal failure. The pathological presentation typically featured Congo red-negative deposits along tubular basement membranes but differed somewhat from the typical "Randall-type" kappa light chain deposition disease: they lacked the prominent glomerulosclerosis pattern often featuring nonamyloid kappa deposits and were associated with cylinders or myeloma casts. Both protein sequences were deduced from those of the corresponding complementary DNAs in the bone marrow plasma cells. For each chain, products of three independent amplifications by polymerase chain reaction were sequenced and found to be identical. BOU and RAC lambda mRNAs had a normal overall structure consisting of Vlambda2 segments rearranged to Jlambda2Clambda2 but displayed a number of unusual features within their primary sequences. These substitutions are likely responsible for changes in light chain conformation that promote their aggregation and deposition along renal tubule basement membranes.