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Currently filtering by tag: Light chain cast nephropathy

Light Chain Cast Nephropathy

A 75-year-old female is found to have a creatinine of 4.0 mg/dL on a routine laboratory examination. At the hospital, a CT scan shows lytic lesions within the skull. A SPEP shows an IgG kappa monoclonal protein. A bone marrow biopsy shows 5% plasma cells. A kidney biopsy is requested to look for monoclonal gammopathy of renal significance. Figure 1 shows a normal glomerulus. Figure 2 shows severe interstitial fibrosis. Figures 3 & 4 show abnormal, PAS negative "stiffened" casts with cellular reaction and fracture. Figures 5 & 6 show kappa and lambda immunofluorescence, respectively. This is a case of...

Diagnose This (November 12, 2018)

What is your diagnosis and what do you need to prove it?           ​ ​   ​   ​ ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​ ​   ​ ​   ​ ​  ...

Twitter Poll (September 6, 2018)

ANSWER: A - Thick ascending limb of the loops of the Henle THP (aka uromodulin) is an 85 -kDa glycoprotein encoded by the UMOD gene in humans.  It’s involved in the pathogenesis of light chain cast nephropathy, urolithiasis, and tubulointerstitial nephritis, in urothelial cytoprotection against UTIs, and in mutations of the THP gene in FJHN and MCKD2. References: Micanovic R, et al. Tamm-Horsfall Protein Regulates Granulopoiesis and Systemic Neutrophil Homeostasis. J Am Soc Nephrol 2015; 26(9): 2172-2182. Serafini-Cessi F, et al. Tamm-Horsfall glycoprotein: biology and clinical relevance. Am J Kidney Dis 2003; 42: 658-676. Nasr SH, et al. Uromodulin storage...

Light Chain Cast Nephropathy with Congo Red Staining

This biopsy was taken from a 60-year-old African American female with a history of diabetes mellitus and hypertension, who presented with acute kidney injury and a serum creatinine of 5.8 mg/dl. Workup revealed an IgA kappa monoclonal band by serum protein electrophoresis. The biopsy shows numerous PAS-pale, focally fractured tubular casts with associated cellular reaction (Fig 1). These casts frequently stained positive for Congo red (Fig 2), and focally showed apple-green birefringence upon polarization. Otherwise, Congo red stain was diffusely negative within the glomeruli, interstitium, vessels, and cytoplasm of tubular epithelium. Immunofluorescence showed kappa light chain restriction of the casts...

Tubular Cast Tutorial

There is a histopathologic spectrum to the casts that can be seen in light chain cast nephropathy. A portion of this spectrum is shown in these photomicrographs of renal biopsies stained with PAS. All three of these cases had casts with light chain restriction by immunofluorescence. Photomicrograph A shows the classic PAS-negative cast with a cellular reaction. The casts in Photomicrograph B have an elongated crystalline appearance. The casts in Photomicrograph C stain weak by PAS and have more of a granular appearance. It is important for the renal pathologist to be aware of this histopathologic spectrum though there is...

Pushing Glass (August 22, 2017)

An 85-year-old gentleman presents to the clinic with nephrotic range proteinuria and a creatinine of 10.0 mg/dl. He reports a 20 lb weight loss over the last 2 months and says that he is having trouble keeping down anything solid. A SPEP and UPEP show a monoclonal kappa band. What is the best diagnosis? a. Light Chain Cast Nephropathy b. Light Chain Deposition Disease c. Light Chain Tubulopathy d. AL-Type Amyloidosis The correct answer is a (light chain cast nephropathy). The biopsy shows several fractured casts with a cell reaction. The casts are PAS-negative and “chatter” marks are identified. The...

Extramedullary Hematopoiesis

This renal biopsy shows extramedullary hematopoiesis (EMH), which is the presence of hematopoietic elements (erythroid, myeloid, and/or megakaryocytic) found outside of the bone marrow. The larger circle contains mostly erythroid precursors and the arrow identifies an immature megakaryocyte. Generally, the histologic differential diagnosis includes acute interstitial nephritis (erythroid precursors may be confused with mature inactive lymphocytes) and even some types of lymphoma (megakaryocytes may resemble atypical or malignant lymphoid cells). In difficult cases, lineage-specific immunohistochemical stains can be used to confirm the presence of hematopoietic cells. Recognizing EMH is important because it often signifies impaired bone marrow function due to...

Amyloid Casts

The differential diagnosis of acute renal failure in patients with multiple myeloma includes light chain cast nephropathy, amyloidosis, and monoclonal immunoglobulin deposition disease, among other possibilities. On occasion, patients with light chain cast nephropathy have large lamellated silver-positive casts with prominent peripheral spicules (Figure 1 and 2) instead of the more characteristic fractured and refractile PAS-negative casts. Such casts usually exhibit light chain restriction by immunofluorescence, and they have been designated in the literature as “intratubular amyloid” or “tubular amyloid casts” because they show congophilia and apple-green birefringence with polarized light (Figure 3). However, in the absence of glomerular, vascular,...

Light Chain Cast Nephropathy

Immunofluorescence staining with kappa light chain and lambda light chain antibodies shows negative kappa in casts that are lambda positive in serial section. Monoclonal light chain staining in atypical casts is characteristic of light chain cast nephropathy (LCCN). In this case, a monoclonal lambda clone is responsible though kappa light chains are the more common cause with a 3 to 1 predominance. These casts are not only tubulotoxic but are also obstructive.

Light Chain Cast Nephropathy

Atypical fractured cast that is pale on PAS stain is suggestive of light chain cast nephropathy (LCCN). Immunofluorescence examination for kappa and lambda light chains is required for diagnosis. LCCN is most often due to a monoclonal kappa rather than lambda clone (~3:1) that is filtered by the glomeruli but accumulates in distal portions of the nephron.  In combination with Tamm-Horsfall protein, they are cytotoxic and obstructive.