Original Article
Split Viewer
Blood Res 2023; 58(1):
Published online March 31, 2023
https://doi.org/10.5045/br.2023.2022232
© The Korean Society of Hematology
Evaluation of laboratory diagnostic tests for light-chain clonality and bone marrow findings in AL amyloidosis
Correspondence to : Chan-Jeoung Park, M.D., Ph.D.
Department of Laboratory Medicine, Asan Medical Center and University of Ulsan College of Medicine, 88 Olympic-ro 43 gil, Songpa-gu, Seoul 05505, Korea
E-mail: cjpark@amc.seoul.kr
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background
Light-chain amyloidosis (AL) is the most common form of systemic amyloidosis. This study aimed to evaluate the usefulness of laboratory tests for light-chain clonality and bone marrow (BM) findings in AL amyloidosis.
Methods
We retrospectively enrolled patients newly diagnosed with AL amyloidosis on pathological examination who underwent a BM biopsy. Laboratory test data for light-chain clonality were collected and compared. Amyloid deposits were identified with H&E, Congo red, and PAS stains.
Results
We reviewed 98 patients with AL amyloidosis. Light chain clonality (λ, 64 cases; κ, 34 cases) was detected by serum immunofixation electrophoresis (IFE) (63.3%), urine IFE (70.8%), serum protein electrophoresis (PEP) (44.9%), urine PEP (44.8%), serum free light chain (SFLC) ratio (79.5%), and BM immunohistochemistry (IHC) (85.7%). Flow cytometric (FCM) assay identified aberrant BM plasma cells in 92.9% of cases. BM amyloid deposits were identified in 35 of the 98 cases (35.7%); 71.4% (25/35) were Congo red-positive, and 100.0% (35/35) were PAS-positive.
Conclusion
Laboratory tests for detecting light-chain clonality in AL amyloidosis in order of sensitivity include FCM assay for aberrant plasma cells, IHC for light chains on BM biopsy or clot section, SFLC ratio, and serum and urine IFE. Congo red staining of BM samples remains an important tool for identifying amyloid deposits in BM. Periodic acid-Schiff (PAS) staining can be useful in diagnosing some cases of Congo red-negative amyloidosis.
Graphical Abstract
Keywords: Light-chain (AL) amyloidosis, Monoclonality, Bone marrow findings, Serum free light chain ratio, Immunohistochemistry, Flow cytometry
PDF
Standard view
Export citation
Share Article
Original Article
Blood Res 2023; 58(1): 71-76
Published online March 31, 2023 https://doi.org/10.5045/br.2023.2022232
Copyright © The Korean Society of Hematology.
Evaluation of laboratory diagnostic tests for light-chain clonality and bone marrow findings in AL amyloidosis
Taegeun Lee1, Chan-Jeoung Park1, Miyoung Kim1, Young-Uk Cho1, Seongsoo Jang1, Sang-Hyun Hwang1, Jung-Hee Lee2, Dok Hyun Yoon3
Departments of 1Laboratory Medicine, 2Hematology, and 3Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Correspondence to:Chan-Jeoung Park, M.D., Ph.D.
Department of Laboratory Medicine, Asan Medical Center and University of Ulsan College of Medicine, 88 Olympic-ro 43 gil, Songpa-gu, Seoul 05505, Korea
E-mail: cjpark@amc.seoul.kr
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background
Light-chain amyloidosis (AL) is the most common form of systemic amyloidosis. This study aimed to evaluate the usefulness of laboratory tests for light-chain clonality and bone marrow (BM) findings in AL amyloidosis.
Methods
We retrospectively enrolled patients newly diagnosed with AL amyloidosis on pathological examination who underwent a BM biopsy. Laboratory test data for light-chain clonality were collected and compared. Amyloid deposits were identified with H&E, Congo red, and PAS stains.
Results
We reviewed 98 patients with AL amyloidosis. Light chain clonality (λ, 64 cases; κ, 34 cases) was detected by serum immunofixation electrophoresis (IFE) (63.3%), urine IFE (70.8%), serum protein electrophoresis (PEP) (44.9%), urine PEP (44.8%), serum free light chain (SFLC) ratio (79.5%), and BM immunohistochemistry (IHC) (85.7%). Flow cytometric (FCM) assay identified aberrant BM plasma cells in 92.9% of cases. BM amyloid deposits were identified in 35 of the 98 cases (35.7%); 71.4% (25/35) were Congo red-positive, and 100.0% (35/35) were PAS-positive.
Conclusion
Laboratory tests for detecting light-chain clonality in AL amyloidosis in order of sensitivity include FCM assay for aberrant plasma cells, IHC for light chains on BM biopsy or clot section, SFLC ratio, and serum and urine IFE. Congo red staining of BM samples remains an important tool for identifying amyloid deposits in BM. Periodic acid-Schiff (PAS) staining can be useful in diagnosing some cases of Congo red-negative amyloidosis.
Keywords: Light-chain (AL) amyloidosis, Monoclonality, Bone marrow findings, Serum free light chain ratio, Immunohistochemistry, Flow cytometry
-
Table 1 . Bone marrow and related laboratory findings according to bone marrow involvement in 98 cases of AL amyloidosis..
Parameters Bone marrow involved patients (N=35) Bone marrow non-involved patients (N=63) P κ/λ clonalitya) 8/27 26/37 0.067 % plasma cells in bone marrow, mean (range) 8.4 (1.2–49.2) 11.0 (0.0–92.4) 0.360b) M-component detection by serum and urine protein electrophoresis 57.1% (20/35) 60.3% (38/63) 0.759 Monoclonality detection by serum and urine immunofixation electrophoresis 80.0% (28/35) 79.4% (50/63) 0.940 Abnormal serum free light chain ratio 91.2% (31/34) 72.2% (39/54) 0.032 Monoclonality detected by immunohistochemistry 82.9% (29/35) 87.3% (55/63) 0.547 Aberrant plasma cells by flow cytometric assay 93.3% (14/15) 92.6% (25/27) 1.000c) a)The number of cases which showed κ or λ clonality. b)The Mann-Whitney U test was used for this comparison. c)Fisher’s exact test was used for this comparison, and the Chi-squared test was used for other comparisons of categorical data..
-
Table 2 . The discrepancies between laboratory tests detecting light-chain clonality and aberrant plasma cells by flow cytometric assay..
Cases N Plasma cell % κ/λ clonality IFE (+) SFLC ratio (Abn) IHC (+) FCM assay (+) IFE (-) 20 2.5 (0.8–52.0) 15/5 NA 10/16 17/20 3/3 SFLC ratio (N) 18 5.1 (1.2–26.8) 5/13 12/18 NA 15/18 7/7 IHC (-) 14 4.0 (0–18.8) 1/13 11/14 13/13 NA 1/3 FCM assay (-) 3 6.8 (3.2–9.6) 0/3 3/3 3/3 1/3 NA Abbreviations: Abn, abnormal; FCM, flow cytometric; IFE, immunofixation electrophoresis; IHC, immunohistochemistry; N, normal; NA, not applicable; SFLC, serum free light chain..
-
Table 3 . Amyloid deposition in bone marrow biopsies or clot sections in 98 cases of AL amyloidosis..
Amyloid deposit gradea) Cases (N=98) % plasma cells,
median (range)λ (N=64) κ (N=34) P Bone marrow 0.887b) 0 63 (64.3%) 11.0 (0.0–92.4) 37 26 1+ 11 (11.2%) 5.6 (1.2–27.2) 8 3 2+ 12 (12.2%) 8.2 (3.6–49.2) 9 3 3+ 12 (12.2%) 14.3 (2.4–35.0) 10 2 a)Amyloid deposit grade: 1+, blood vessels only; 2+, interstitial deposition of ≤2 high-power fields; 3+, interstitial deposition of >2 high-power fields. b)Fisher’s exact test was used for this comparison..
-
Table 4 . Amyloidosis detection methods and bone marrow findings in 35 cases of AL amyloidosis with bone marrow involvement..
N 22 3 10 Detection method Congo red stain by polarizing microscopy Positive Negative Negative Congo red stain by light microscopy Positive Positive Negative PAS stain Positive Positive Positive Amyloid deposit grade scorea) Median (range) 2+ (1+–3+) 2+ (1+–3+) 2+ (1+–3+) % plasma cells in bone marrow Median (range) 7.6 (1.2–49.2) 18.0 (2.8–23.4) 8.2 (1.6–35.0) a)Amyloid deposit grade: 1+, blood vessels only; 2+, interstitial deposition of ≤2 high-power fields; 3+, interstitial deposition of >2 high-power fields..
Article Tools
Stats or Metrics
Share this article on
Related articles in BR
-
Peripheral T-cell lymphoma, NOS in bone marrow and heart
Hye Won Lee and Ja Young Lee
Blood Res 2024; 59(): -
Relevance of flow cytometric categorization and end-of-induction measurable residual disease assessment in pediatric and adult T-lymphoblastic leukemia patients
Karthik Bommannan, Jhansi Rani Arumugam, Venkatraman Radhakrishnan, Jayachandran Perumal Kalaiyarasi, Parathan Karunakaran, Nikita Mehra, Tenali Gnana Sagar, Shirley Sundersingh
Blood Res 2022; 57(3): 175-196 -
Basic immunohistochemistry for lymphoma diagnosis
Junhun Cho
Blood Res 2022; 57(S1): S55-S61
