Staining For Kappa Light Chains Research Articles

Rapidly Progressive Renal Failure in Young Adult: An Atypical Presentation of Multiple Myeloma - A Case Report

Introduction: Patients frequently present with renal impairment that does not fit the criteria for acute kidney injury or chronic kidney disease. This condition, known as rapidly progressive renal failure (RPRF), encompasses a diverse range of clinical syndromes characterized by the progressive renal impairment over days to weeks. Case Report: We present a case of a 37-year-old male with a short history of uremic symptoms and decreased urine output with no significant history or examination findings except pallor. The patient had a creatinine of 1.6 mg/dL in April 2022, rising to 4.4 mg/dL, then 11.6 mg/dL during May, 17.6 mg/dL in June, presented to us with a creatinine of 24.6 mg/dL, with normal kidney size and corticomedullary differentiation (CMD). Beta-2-microglobulin was elevated, and renal biopsy showed features suggestive of multiple myeloma (MM). Atypical appearing tubular casts showing 3+ patternless staining for kappa light chains and negativity for lambda light chains were observed. The patient was started on chemotherapy for MM, and renal function was gradually improving. Conclusion: Renal failure as the sole presentation of MM is rare, especially in young adults. This case emphasizes an atypical RPRF, particularly given the patient’s young age.

Clinic-pathological characteristics of rare tubulointerstitial diseases.

Tubulointerstitial diseases is one of the common causes of renal dysfunction. Some rare pathological types are easy to be misdiagnosed and missedly diagnosed because of their low prevalence and relatively insufficient understanding, which affects the treatment and prognosis of patients. This study aims to explore clinical manifestations and pathological characteristics of several rare tubulointerstitial diseases, and therefore to improve their diagnosis and treatment. A total of 9 363 patients diagnosed by renal biopsy in the Department of Nephrology, Second Xiangya Hospital, Central South University from November 2011 to September 2021 were selected. Six cases of light chain cast nephropathy (LCCN), 2 cases of light chain proximal tubulopathy (LCPT), 1 case of LCCN with LCPT, 4 cases of genetic tubulointerstitial disease, and 6 cases of non-genetic related tubulointerstitial lesion were screened out, and their clinical manifestations and renal biopsy pathological results were collected, compared, and analyzed. Patients with LCCN presented with mild to moderate anemia, microscopic hematuria, and mild to moderate proteinuria. Compared with patients with LCPT, proteinuria and anemia were more prominent in patients with LCCN. Five patients with LCCN and 2 patients with LCPT had elevated serum free kappa light chain. Five patients with LCCN presented clinically with acute kidney injury (AKI). Two patients with LCPT and 1 patient with LCCN and LCPT showed CKD combined with AKI, and 1 LCPT patient presented with typical Fanconi syndrome (FS). Five patients with LCCN, 2 patients with LCPT, and 1 patient with LCCN and LCPT were diagnosed with multiple myeloma. Five patients with LCCN had kappa light chain restriction in tubules on immunofluorescence and a "fractured" protein casts with pale periodic acid-Schiff (PAS) staining on light microscopy. Immunohistochemical staining of 2 LCPT patients showed strongly positive kappa light chain staining in the proximal tubular epithelial cells. And monoclonal light chain crystals in crystalline LCPT and abnormal lysosomes and different morphological inclusion bodies in noncrystalline LCPT were observed under the electron microscope. Six patients with LCCN were mainly treated by chemotherapy. Renal function was deteriorated in 1 patient, was stable in 4 patients, and was improved in 1 patient. Two patients with LCPT improved their renal function after chemotherapy. Four patients with genetic tubulointerstitial disease were clinically presented as CKD, mostly mild proteinuria, with or without microscopic hematuria, and also presented with hyperuricemia, urine glucose under normal blood glucose, anemia, polycystic kidneys. Only 1 case had a clear family history, and the diagnosis was mainly based on renal pathological characteristics and genetic testing. Compared with patients with non-genetic related tubulointerstitial lesion, patients with genetic tubulointerstitial disease had an earlier age of onset, higher blood uric acid, lower Hb and estiated glomemlar fitration (eGFR), and less edema and hypertension. Renal pathology of genetic tubulointerstitial disease presented tubular atrophy and interstitial fibrosis, abnormal tubular dilation, glomerular capsuledilation, and glomerular capillary loop shrinkage. Glomerular dysplasia and varying degrees of glomerular sclerosis were observed. Genetic tubulointerstitial disease patients were mainly treated with enteral dialysis, hypouricemic and hypoglycemic treatment. Two genetic tubulointerstitial disease patients had significantly deteriorated renal function, and 2 patients had stable renal function. Patients with AKI or FS, who present serum immunofixation electrophoresis and/or serum free kappa light chain abnormalities, should be alert to LCCN or LCPT. Renal biopsy is a critical detection for diagnosis of LCCN and LCPT. Chemotherapy and stem cell transplantation could delay progression of renal function in patients with LCCN and LCPT. If the non-atrophic area of the renal interstitium presents glomerular capsule dilatation, glomerular capillary loop shrinkage, and abnormal tubular dilatation under the light microscopy, genetic tubulointerstitial disease might be considered, which should be traced to family history and can be diagnosed by genetic testing.

Monoclonal glomerulopathy with features of cryoglobulinemic glomerulopathy in murine multiple myeloma model

ABSTRACT In vivo and animal models of monoclonal light chain-associated renal diseases are limited. The Vk*MYC transgenic model with multiple myeloma in 50–70 weeks old mice with renal involvement has been reported before, but detailed renal pathologic changes have not been well documented. This study fully investigated pathologic changes in the kidneys of Vk*MYC transgenic model using light microscopy, immunofluorescence stains for kappa and lambda light chains, and electron microscopy. Compared to the kidneys of wild-type mice, the kidneys of transgenic mice showed either mesangial segmental expansion, some with associated hypercellularity, and/or thrombotic obstruction of glomerular capillaries. The glomeruli revealed stronger lambda staining than kappa light chain staining. Six out of 12 kidneys from transgenic mice showed abundant electron-dense deposits when examined ultrastructurally. The deposits were located in glomerular capillary lumina in three cases. Large luminal and subendothelial deposits were characterized by randomly disposed microtubular structures measuring up to 16 nm in diameter, with overall features most consistent with cryoglobulins. In summary, about 50% of kidneys from the Vk*MYC mice with myeloma had features most consistent with monoclonal cryoglobulinemic glomerulopathy.

Light chain deposition disease in a postrenal transplant patient

The morphological spectrum of light chain deposition disease (LCDD) may range from normal glomerular morphology to mesangio-proliferative to mesangio-capillary to nodular sclerosing patterns. Due to the inconsistencies regarding treatment and the universally poor graft outcome of post-transplant LCDD, it is imperative to maintain a high index of suspicion and perform relevant investigations for clinching this diagnosis. A 40-year-old lady was diagnosed as a case of membrano-proliferative glomerulonephritis 3 years back, for which she underwent a live unrelated renal allograft transplant. Postoperative period was complicated by an acute rise in serum creatinine on the 21st postoperative day. Biopsy showed patchy acute cortical necrosis, which responded to conservative management. The present admission was for renal failure and subnephrotic proteinuria. A kidney biopsy was performed, and all the 14 glomeruli examined showed a mesangiocapillary pattern of glomerular injury with cellular nodule formation in some. The nodules were PAS and Congo red negative. Immunofluorescence showed glomerular and tubular basement staining for Kappa light chains only. Electron microscopy showed the characteristic granular deposits in subendothelial location in the glomerulus, and in tubular basement membranes, thus confirming the diagnosis of LCDD. Membranoproliferative pattern of glomerular injury in the pre- and posttransplant setting has a wide range of differential diagnoses; LCDD being one of them.

Marked improvement by high-dose chemotherapy and autologous stem cell transplantation in a case of light chain deposition disease

A 55-year-old woman presented with heavy proteinuria (6.2 g/day) in April 2007. Because monoclonal IgG-k was detected in serum and urine samples, bone marrow aspiration and renal biopsy were performed. She was diagnosed with plasma cell dyscrasia because a bone marrow aspiration specimen showed plasma cells at 6.1%. Renal tissues revealed the formation of nodular glomerulosclerosis which was negative for Congo-red staining. Renal immunohistochemistry showed positive staining for kappa light chains in the nodular lesions, proximal tubules and part of Bowman's capsules. Her renal involvement was diagnosed as light chain deposition disease. Proteinuria disappeared and renal function stabilized after high-dose chemotherapy and autologous stem cell transplantation. It appears that an early initiation of active therapy such as high-dose chemotherapy and autologous stem cell transplantation may be beneficial for patients with light chain deposition disease.

Sinonasal extramedullary plasmacytoma

An 81-year-old male presented with a four-month progressive right-sided nasal obstruction and epistaxis due to a polyp. He received antibiotics and intranasal steroid inhalers, without improvement. He had no known history of paranasal sinus disease or allergies. Rhinoscopy revealed an amber polypoid mass with a clear surface, filling the entire nasal cavity. Comprehensive examination was otherwise unremarkable. CT scan demonstrated opacification of the right nasal fossa and the maxillary sinus, without bony erosion. Surgical pathology revealed a polypoid structure lined by attenuated cuboidal epithelium, while its core was massively infiltrated by a relatively monotonous population of smallto medium-sized cells (Fig 1A). The lesional cells illustrated a diffuse membranous staining for CD138 (Fig 1B); further kappa light chain staining highlighted their cytoplasm. Pathologic diagnosis was sinonasal (extramedullary) plasmacytoma. This rare monoclonal gammopathy presents in the head and neck region in 80 percent of the cases, predominantly in the sinonasal cavities. Patients are typically older (median age: 55 yrs), and 75 percent are males. Variable symptoms include nasal obstruction, recurrent rhinosinusitis, and epistaxis. This abnormal accumulation of plasmoblasts is triggered by chemotaxis of immune system cells to the sinonasal mucosa, which leads to an extensive inflammatory reaction and angiogenesis. Presentation can be either an isolated solitary mass or in association with other gammopathies, most commonly multiple myeloma. Differentiation of extramedullary plasmacytoma from other hematological malignancies, such as extranodal marginal zone lymphomas or low-grade lymphomas with plasmacytoid differentiation, is made by immunohistochemistry and flow cytometry. Plasma cell tumors express both CD138 and monoclonal cytoplasmic light chain, either k or l. Treatment includes radiotherapy and/or surgery, with a similar recurrence rate of 12.5 percent. Several authors consider the combination of these modalities as the preferred treatment. The high affinity to the sinonasal tract can be attributed to the rich lymphoid deposits and their role in humoral immunity. The work received the approval of the Institutional Review Board.

Primary Sclerosing Cholangitis in Association with Multiple Myeloma

Purpose: We report the second known case of multiple myeloma (MM) associated with primary sclerosing cholangitis (PSC). Methods: CASE REPORT Results: A 57-year-old man presented with a 6 month history of jaundice with total bilirubin of 6.3 mg/dL, associated with increased alkaline phosphatase to 800 unit/L. Workup included ERCP (Fig. 1) which confirmed PSC and biopsy confirming cirrhosis. In the course of his pre-transplant evaluation, he developed marked malnutrition with a decrease in serum albumin from 3.6 to 2.0 g/dL and hypercalcemia. Lytic lesions were identified in the humerus on routine X-rays. A monoclonal IgG -kappa restricted serum immunofixation and significant kappa light chains in the urine (1790 mg/L) were found. Figure 2 is a high power photomicrograph of H & E stained marrow clot section from a biopsy of the humeral lesion, showing marrow replacement by plasma cells- some with binucleation. The inset shows strong staining for kappa light chains, confirming that lesion is monoclonal for kappa light chains- consistent with monoclonal plasma cell dyscrasia (PCD). Given the confirmation of multiple myeloma and advanced cirrhosis, palliative care was initiated. Conclusion: This case is the second report to suggest the possible association of MM with PSC. PCD encompases a number of disorders with MM being the most serious. PCD is often associated with other chronic liver diseases such as chronic active hepatitis, autoimmune hepatitis, and primary biliary cirrhosis. It is thought that chronic antigenic stimulation by the cirrhotic liver selects B cell clones which may eventually become malignant. This case highlights the possible connection between MM and PSC.[figure1][figure2]FigureFigure

Immunofluorescence on pronase-digested paraffin sections: A valuable salvage technique for renal biopsies

Direct immunofluorescence (IF) on frozen tissue is the method of choice for the study of medical renal diseases. When no glomeruli are available, IF can be performed on the formalin-fixed paraffin-embedded tissue allocated for light microscopy after antigen retrieval with proteases. In this study, the results of IF on frozen tissue (IF-F) and on deparaffinized, pronase-treated tissue (IF-P) were compared in 71 renal biopsies representing 12 major renal diseases. Using IF-P, diagnostic findings were obtained in 100% of cases of lupus nephritis, acute post-infectious glomerulonephritis, cryoglobulinemic glomerulonephritis, fibrillary glomerulonephritis, primary amyloidosis, myeloma cast nephropathy, and light-chain Fanconi syndrome (LCFS), 88% of cases of immunoglobulin (Ig)A nephropathy, 80% of cases of light-chain deposition disease, 60% of cases of membranoproliferative glomerulonephritis type 1, 50% of cases of idiopathic membranous glomerulopathy (MGN) and 20% of cases of anti-glomerular basement membrane (GBM) disease. IF-P was less sensitive than IF-F for the detection of C3 in all disease categories and for the detection of IgG in cases of MGN and anti-GBM disease. The diagnostic kappa light-chain staining was demonstrated in 100% of cases of LCFS by IF-P versus 40% by IF-F. We conclude that IF-P is a valuable salvage immunohistochemical technique for renal biopsies lacking adequate cortical sampling for IF-F, and is superior to IF-F for the diagnosis of LCFS.

Expanding the pathologic spectrum of light chain deposition disease: a rare variant with clinical follow-up of 7 years

We report an unusual histologic manifestation of light chain deposition disease in a 69-year-old female patient, who presented with nephrotic syndrome and an increased serum creatinine. The renal biopsy findings by light and electron microscopy suggested a glomerulonephritis with massive immune-complex deposition, such as lupus nephritis. However, the overall clinical scenario was inconsistent with lupus. Subsequent tests revealed multiple myeloma confirmed by bone marrow biopsy and identification of a monoclonal kappa light chain immunoglobulin by serum and urine immunoelectrophoresis and immunofixation. Additional immunohistochemistry of the first biopsy also demonstrated strong kappa light chain staining of the glomerular capillary walls and mesangium but not lambda light chain or IgG staining. The patient responded well to therapy and was asymptomatic until nearly 7 years later. A repeat biopsy revealed similar findings to the first biopsy with the addition of immunofluorescence microscopy, which confirmed the prominent kappa light chain staining of the glomeruli, tubular basement membranes, and interstitium with corresponding electron-dense deposits visualized by electron microscopy. This case represents an unusual histologic variant of light chain deposition disease, which to our knowledge has not been previously described and further expands the wide clinicopathologic spectrum within the diagnostic entity of light chain deposition disease.

Immunotactoid glomerulopathy with microtubular deposits, with reference to the characteristics of Japanese cases

We present the case of a 69-year-old man with nephrotic syndrome and renal insufficiency, who developed lobular glomerulonephritis. An electron microscopy examination of a renal biopsy showed microtubular structures of 24 nm in diameter in the subendothelial space and the paramesangial area. These deposits were PAS-positive and Congo red-negative, and revealed predominantly positive staining for kappa light chain. There was no evidence of diseases with highly organized glomerular deposits, such as amyloidosis, cryoglobulinemia, systemic lupus erythematosus or paraproteinemia. Therefore, the patient was diagnosed to have immunotactoid glomerulopathy (ITG). During a seven-year course he has not developed any disease known to be associated with organized glomerular immune deposits. Hence, we believe ITG occurred as a primary glomerular disease in this case. We also highlight cases of ITG with microtubular deposits that have been reported in Japan, compare these cases to previous reports, and show that the characteristics of the Japanese cases are male predominance; a high incidence of membranoproliferative glomerulonephritis (MPGN); a low incidence of monoclonal gammopathy and hematological malignancies and a higher incidence of hypocomplementemia.

Crystalline Inclusions in the Glomerular Podocytes in a Patient With Benign Monoclonal Gammopathy and Focal Segmental Glomerulosclerosis

We report a case of a 40-year-old woman with benign monoclonal gammopathy who developed focal segmental glomerulosclerosis associated with widespread deposition of large crystalline inclusions in the glomerular podocytes. Electron microscopy showed that the crystalline structures were electron dense and needle shaped or polygonal. At a higher magnification, they were seen to be surrounded by unit membranes and to feature a longitudinal filamentous substructure. These inclusions showed positive immunohistochemical staining for kappa light chain. Clinically, the patient had shown nephrotic syndrome on the first medical examination, and later revealed chronic renal failure and monoclonal gammopathy of the immunoglobulin G kappa type, but no evidence of multiple myeloma or other lymphoproliferative diseases. This patient seems to have had a rare form of glomerular involvement associated with benign monoclonal gammopathy.

Single light chain subclass (kappa chain) immunoglobulin deposition in glomerulonephritis

Renal glomerular disease characterized by the deposition of immunoglobulin light chains or monoclonal immunoglobulins was demonstrated by immunofluorescence microscopy in 11 patients. The most common histopathologic findings were those of mesangiocapillary glomerulonephritis, but considerable variability was observed. Lesions resembling diabetic glomerulosclerosis and amyloidosis were seen in some patients. Immunofluorescence findings in seven patients showed concomitant, equally intense staining for kappa light chain and immunoglobulin heavy chain (IgG or IgA), indicative of monoclonal immunoglobulin deposition. Specimens in the remaining cases stained predominantly for kappa light chain alone. In six cases the histologic and ultrastructural pattern was similar to that of type I mesangiocapillary glomerulonephritis. In three cases linear deposits were present, predominantly in subendothelial and inner glomerular basement membranes and, to a lesser degree, in mesangial locations, as in type II mesangiocapillary glomerulonephritis. In one of the latter cases dense deposits were intermixed with aggregates of amorphous fibrillar material indistinguishable from amyloid. In two cases involving IgA kappa chain deposition the histologic and ultrastructural appearance was that of mesangial glomerulonephritis. Considerable heterogeneity was found in the clinical features of the patient population. Specific clinical or serologic parameters for this disease could not be identified. Only one patient had an associated lymphoplasmacytic disorder. After follow-up periods ranging from six months to 17 years, all of the patients were alive, including four who had progressed to end-stage renal disease and required dialysis. Two of the latter patients underwent successful renal transplantation; one had been alive for five years and the other for three months without evidence of recurrence of the renal disease at the last follow-up examination.