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  Table of Contents    
CASE REPORT  
Year : 2014  |  Volume : 57  |  Issue : 4  |  Page : 629-631
Unique morphology of intratubular light chain casts in multiple myeloma: The amyloid cast nephropathy


1 Department of Histopathology, National Reference Laboratory, Dr. Lal Path Labs, New Delhi, India
2 Department of Pathology, Manav Rachna Dental Collge, Faridabad, Haryana, India
3 Department of Nephrology, Saroj Hospital, Rohini, New Delhi, India

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Date of Web Publication11-Oct-2014
 

   Abstract 

Cast nephropathy is the most frequent pattern of renal involvement in multiple myeloma characterized by presence of tubular casts with characteristic morphology that are composed of monotypic (either kappa or lambda) light chains as seen by immunofluorescence microscopy. Rarely these casts may show evidence of amyloidogenesis and assume a unique morphology, which needs to be appreciated for arriving at accurate diagnosis. We present the case of an elderly male presenting with features of acute kidney injury and detected with extensive inspissation of intratubular casts with lambda light chain restriction and a unique morphology with spiculated congophilic periphery. Further investigations confirmed the presence of systemic myeloma. Presence of intratubular amyloid casts is a rare occurrence which needs to be recognized by the pathologist and forms a vital element in timely diagnosis of the systemic disease which often presents with renal involvement.

Keywords: Cast nephropathy, intratubular amyloid, multiple myeloma

How to cite this article:
Sharma A, Bansal S, Jain R. Unique morphology of intratubular light chain casts in multiple myeloma: The amyloid cast nephropathy . Indian J Pathol Microbiol 2014;57:629-31

How to cite this URL:
Sharma A, Bansal S, Jain R. Unique morphology of intratubular light chain casts in multiple myeloma: The amyloid cast nephropathy . Indian J Pathol Microbiol [serial online] 2014 [cited 2019 Dec 9];57:629-31. Available from: http://www.ijpmonline.org/text.asp?2014/57/4/629/142712



   Background Top


Multiple myeloma (MM) is a plasma cell dyscrasia that accounts for almost 10% of all hematologic malignancies. [1] Cast nephropathy is the most frequent pattern of renal involvement in MM characterized by the inspissation of tubular casts with characteristic morphology in the distal nephron that are composed of monotypic (either kappa or lambda) light chains as seen by immunofluorescence microscopy. The casts contain either immunoglobulin (Ig) light chain, Ig, or other serum proteins, including Tamm-Horsfall glycoprotein, often show a characteristic brittle appearance with "fracture planes" and also elicit variable epithelial or inflammatory cell response. Rarely the monoclonal paraprotein may exhibit amyloidogenesis and produce tubular casts with a unique morphologic appearance, quite distinct from the usual light chain casts. We present the case of an elderly male patient presenting with renal failure, mild proteinuria and found to have cast nephropathy with tubular casts composed predominantly of amyloidogenic paraprotein showing lambda light chain restriction.


   Case report Top


The 60-year-old male previously in good health, presented with complaints of nausea, vomiting mild pedal edema for 2 weeks. There was no history of hypertension, diabetes mellitus, joint pains, recent fever, sore throat, skin rashes or macroscopic hematuria. No significant drug/therapeutic history and no history of previous major illness or surgeries were elicited. On examination, there was Grade 1 pallor, mild pedal edema and blood pressure was140/80 mm Hg (not on drugs). Systemic examination revealed right-sided fluid thrill. Urine dipstick examination revealed 2 + protein, absent sugar and microscopy showed 10-15 pus cells/hpf without any red blood cells. Important investigative findings at presentation are enumerated in [Table 1]. In view of rapidly rising creatinine and unexplained renal failure, renal biopsy was performed.
Table 1: Selected investigative findings at presentation

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Light microscopic examination of renal biopsy showed features of severe tubular injury with epithelial simplification, loss of brush borders, focal chronic interstitial inflammation and inspissation of several variably sized casts in tubular lumina including few hyaline and granular casts. Many of the tubular casts showed a unique morphology with a central paler area or nidus and "spiculated" periphery, which was periodic acid-Schiff positive, argyrophilic, congophilic and blue with Masson's' trichrome stain [Figure 1]a-d. Very occasional "brittle" appearing casts with "fractured" appearance and eliciting mild epithelial cell reaction without evidence of amyloidogenesis were also noted. Both intratubular amyloid casts and the brittle casts showed lambda light chain restriction on immunofluorescence examination [Figure 2]. Glomeruli were histologically unremarkable and showed no evidence of amyloid deposition or significant Ig, complement or light chain deposits in immunofluorescence studies. No Ig (heavy chain) or light chain (kappa or lambda) deposits were seen along the tubular basement membranes. Since no tissue was initially sampled for electron microscopy, the paraffin-embedded remaining renal biopsy tissue was reprocessed for ultrastructural studies and showed tubular casts with randomly branching fibrils, confirming amyloid deposition [Figure 2]c. Further investigations showed M band on serum electrophoresis and bone marrow plasmacytosis (30%), without evidence of amyloid deposition. Serum free light chain assays showed markedly elevated lambda light chains: 79.5 mg/L (reference range: 5.7-26.3 mg/L), serum-free kappa light chains; 1.1 (reference range: 3.3-19.4 mg/L) and serum free light chain kappa/lambda ratio of 0.01 (reference range: 0.26-1.65 mg/L). No bony lytic lesions were detected on a skeletal survey. A final diagnosis of myeloma cast nephropathy with predominantly amyloidogenic tubular casts showing lambda light chain restriction was made.
Figure 1: Composite photomicrograph showing tubular casts with a pale nidus in H and E stained sections (a) and a spiculated periphery which shows argyrophilic "spikes" in silver methenamine stained sections (b) and are blue with Masson's trichrome stain (c) Periphery of the casts is congophilic (d) and shows greenish birefringence when viewed under polarized lights (inset), suggestive of amyloid formation (All images ×200)

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Figure 2: Composite micrograph showing negativity for kappa light chains (a) and intense positivity for lambda light chains (b) in the intratubular casts (Direct immunofluorescence ×200). Ultrastructural examination shows irregularly branching fibrils 7-10 nm in diameter (c) Consistent with amyloid (Uranyl acetate & lead citrate × 80000

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   Disucssion Top


The annual incidence of MM is 4.3/100,000 people, but the incidence ranges from 1/100,000 for people who are 40-49 years of age to 49/100,000 population for those who are >80 years of age. [2],[3] The spectrum of renal lesions seen in patients with myeloma include "myeloma kidney," or cast nephropathy; Amyloid light chain (AL) amyloidosis; monoclonal Ig deposition disease (MIDD); and, less frequently, cryoglobulinemic glomerulonephritis and proliferative glomerulonephritis. [4] While the renal pathology of cast nephropathy, MIDD, and amyloidosis is diverse, the initial pathogenetic event is the production of an abnormal Ig fragment (usually an Ig light chain) by a clone of neoplastic plasma cells in the bone marrow.

The kidneys of patients with MM and renal insufficiency show a variety of pathologic lesions, most common being cast nephropathy. The diagnosis of cast nephropathy is based on the demonstration of tubular casts in the distal nephron that are composed of Ig light chains [Table 2]. Free kappa and lambda light chains have molecular weights of 22.5 k Dalton and 45 k Dalton respectively are easily filtered across the glomerular filtration barrier. These filtered light chains form tubular casts by co-aggregating with the carbohydrate moiety of Tamm-Horsfall glycoprotein, which is produced in the thick ascending limb of the loop of Henle. Factors that influence cast formation include the type and concentration of Bence Jones glycoprotein, serum calcium concentration, pH, sodium chloride concentration, tubular flow rate, dehydration, hypercalcemia etc. [5],[6] Depending upon the complex interplay of aforementioned factors, the light chains may form the usual "brittle" or "fractured" casts or may lodge themselves in tubular epithelial cells or lumina as needle/rhomboid or rectangular shaped crystals in patients with light chain associated Fanconi's syndrome.
Table 2: Morphological characteristics of various tubular casts that may be encountered in renal biopsies of patients with multiple myeloma

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Rarely, the tubular light chain casts show evidence of amyloidogenesis. The presence of tubular amyloid in patients with MM and cast nephropathy is not only rare with only four previous published reports to the best of our knowledge, [7],[8],[9],[10] but also intriguing, as amyloid with a high molecular weight is unlikely to be filtered as such across the glomerular barrier. The casts are presumably formed as a result of conformational changes occurring in the filtered or secreted light chains, rendering them amyloidogenic. The central pale area in these casts is composed of cellular and necrotic debris and occasionally the Tamm-Horsfall glycoprotein, around which the amyloidogenic paraprotein deposits in layers, often giving a "spike" like appearance. Form renal pathologists point of view, knowledge regarding the occurrence of these casts is necessary as they may be the predominant or exclusive type of casts in a given case and can be missed if careful attention is not paid, thereby delaying or preventing an important diagnosis.

 
   References Top

1.
Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med 2004;351:1860-73.  Back to cited text no. 1
    
2.
Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, et al. Cancer statistics, 2005. CA Cancer J Clin 2005;55:10-30.  Back to cited text no. 2
    
3.
Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Melton LJ 3 rd . Incidence of multiple myeloma in Olmsted County, Minnesota: Trend over 6 decades. Cancer 2004;101:2667-74.  Back to cited text no. 3
    
4.
Markowitz GS. Dysproteinemia and the kidney. Adv Anat Pathol 2004;11:49-63.  Back to cited text no. 4
[PUBMED]    
5.
Rota S, Mougenot B, Baudouin B, De Meyer-Brasseur M, Lemaitre V, Michel C, et al. Multiple myeloma and severe renal failure: a clinicopathologic study of outcome and prognosis in 34 patients. Medicine (Baltimore) 1987;66:126-37.  Back to cited text no. 5
[PUBMED]    
6.
Sanders PW. Pathogenesis and treatment of myeloma kidney. J Lab Clin Med 1994;124:484-8.  Back to cited text no. 6
[PUBMED]    
7.
Melato M, Falconieri G, Pascali E, Pezzoli A. Amyloid casts within renal tubules: A singular finding in myelomatosis. Virchows Arch A Pathol Anat Histol 1980;387:133-45.  Back to cited text no. 7
[PUBMED]    
8.
Friman C, Törnroth T, Wegelius O. IgD myeloma associated with multiple extramedullary amyloid-containing tumours and amyloid casts in the renal tubules. Ann Clin Res 1970;2:161-6.  Back to cited text no. 8
    
9.
El-Zoghby Z, Lager D, Gregoire J, Lewin M, Sethi S. Intra-tubular amyloidosis. Kidney Int 2007;72:1282-8.  Back to cited text no. 9
    
10.
Sethi S, Hanna MH, Fervenza FC. Unusual casts in a case of multiple myeloma. Am J Kidney Dis 2009;54:970-4.  Back to cited text no. 10
    

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Correspondence Address:
Alok Sharma
National Reference Laboratory, Dr. Lal Path Labs, Rohini, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.142712

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