Kappa & lambda light chains

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Stains & CD markers
Kappa & lambda light chains

Author: Nat Pernick, M.D.

Editorial Board Members: Alexa J. Siddon, M.D., Brandon Umphress, M.D.

Last author update: 12 July 2024

Last staff update: 12 July 2024

Copyright: 2003-2024, PathologyOutlines.com, Inc.

PubMed Search: Kappa & lambda light chains

Table of Contents

Cite this page: Pernick N. Kappa & lambda light chains. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainskappa.html. Accessed December 22nd, 2024.

Definition / general

Kappa and lambda are immunoglobulin light chains
Restricted expression of either kappa or lambda suggests monoclonality and a neoplastic process
This topic discusses immunohistochemistry (IHC) or in situ hybridization (ISH) for these light chains; see Interference in protein electrophoresis for interferences in the serum measurements of light chains

Essential features

IHC stains or ISH for kappa and lambda light chains are used to establish the clonal or polyclonal nature of plasma cells or lymphocytes
- Reactive lymph nodes produce a mixture of kappa and lambda light chains
- Plasma cell neoplasms and certain lymphomas produce only 1 light chain (kappa or lambda)
- Kappa and lambda IHC are most helpful with plasma cells because they produce significant light chains; staining of lymphocytes is variable
- Light chain proximal tubulopathy features detection of either kappa or lambda light chains or proximal tubular epithelial cells but not both
Light chain IHC (kappa or lambda) can confirm the identity of cells as plasma cells

Terminology

Bence Jones proteins (urinary free light chains): free light chains produced by neoplastic plasma cells in plasma cell myeloma (multiple myeloma) or monoclonal gammopathy of undetermined significance (MGUS) and detected in the urine

Pathophysiology

Kappa chain is encoded by the immunoglobulin kappa (IGK@) locus at 2p11.2 and the lambda chain is encoded by the immunoglobulin lambda (IGL@) locus at 22q11.2 (Wikipedia: Immunoglobulin Light Chain [Accessed 7 May 2024])
Kappa/lambda ratio in serum (the liquid part of blood after coagulation) is usually 2:1
B cells express surface immunoglobulin composed of 2 heavy chains and 2 light chains (either kappa or lambda but not both)
Reactive lymph nodes should produce a mixture of both types, detectable by immunohistochemistry (IHC) or in situ hybridization (ISH)
- Note that a neoplastic process involving other cells may be accompanied by reactive lymphocytes or plasma cells
Lymph nodes with a neoplastic clone (suggestive of lymphoma or a plasma cell neoplasm) produce only 1 type of light chain
Free light chains
- Produced in neoplastic diseases (clonal) and inflammatory diseases (polyclonal)
- In inflammatory diseases, free light chains bind to and activate mast cells, which promotes the inflammation
See also Interference in protein electrophoresis

Diagrams / tables

Images hosted on other servers:

Antibody structure

Clinical features

Many monoclonal therapeutics appear as monoclonal IgG kappa chains by immunofluorescence and interfere with protein electrophoresis results

Interpretation

Staining tends to be membranous for lymphocytes and lymphoproliferative lesions versus cytoplasmic for plasma cells and plasma cell neoplasms

Uses by pathologists

Kappa / lambda IHC or ISH is used to determine clonal status of lymphocytes and plasma cells
- Myeloma, MGUS, plasmacytoma: show monoclonal light chain restriction (i.e., either kappa or lambda), which is useful for diagnosis, particularly if there are abundant neoplastic plasma cells
  - Rare cases of nonproducer nonsecretory myeloma may express no kappa or lambda light chain
- Monoclonal gammopathy of renal significance (MGRS) / paraprotein related kidney disease: includes all kidney diseases caused by any plasma cell or B cell clonal disorder (leukemia / lymphoma) that does not meet the criteria for a neoplasm but produces monoclonal immunoglobulins or light chains
  - For this diagnosis, the light chain restriction exhibited by the clonal deposit in the kidney must be the same as the paraprotein present in blood, bone marrow or lymph node tissue
- Systemic AL amyloidosis: clonal plasma cell disorder in which amyloid is light chain related; the amyloid may occur in association with myeloma
- To diagnose AL type amyloid at various sites based on clonal light chain expression
- Light chain proximal tubulopathy: clonal kappa or lambda (never both) staining of proximal tubular epithelial cells on routine or granular staining on pronase digested immunofluorescence is pathognomonic (J Am Soc Nephrol 2016;27:1555, Mod Pathol 2011;24:1462, BMC Nephrol 2020;21:146)
- Light chain cast nephropathy: clonal staining of casts by immunofluorescence or immunohistochemistry for either kappa or lambda but not both
  - However, only half of the casts in proven light chain cast nephropathy cases stain in a monoclonal pattern (Fogo: Diagnostic Renal Pathology, 4th Edition, 2022)
  - Clonal staining may be absent when casts are present in few numbers focally only or secondary to mutated light chains not recognized by commercial antibodies
- Light chain deposition disease: granular deposits of kappa (80%) or lambda (20%) light chains (not both) along glomerular and tubular basement membranes, in mesangium, vessel walls and interstitium
Immunofluorescence is useful for diagnosis of acute postinfectious glomerulonephritis and IgA nephropathy
Diabetic kidney disease: diffuse linear accentuation of the glomerular basement membrane and tubular basement membrane with IgG, a mixture of kappa and lambda light chains and albumin

Case reports

49 year old woman with a mediastinal mass (thymoma) and a prominent polyclonal plasma cell infiltrate (Am J Clin Pathol 1994;102:199)
49 year old woman, 60 year old woman and 82 year old man with polyclonal B cell lymphocytosis (Cytometry B Clin Cytom 2018;94:953)
56 year old woman with multiple myeloma (type IgG kappa) (J Hematother Stem Cell Res 2001;10:657)
63 year old man, 72 year old man and 73 year old woman with myeloma diagnosed based on renal biopsy, IHC and immunofluorescence for light chains (Indian J Nephrol 2017;27:395)
67 year old woman with anemia, severe renal insufficiency and multiple lytic bone lesions diagnosed with kappa light chain multiple myeloma (Cureus 2021;13:e19131)
69 year old woman with a generalized kappa restricted crystal storing histiocytosis involving the bone marrow and kidney (Ren Fail 2023;45:2145970)
76 year old woman who presented with immunotactoid glomerulopathy concomitant with κ light chain myeloma cast nephropathy (Am J Kidney Dis 2023;81:611)
78 year old woman with chronic lymphocytic leukemia (CLL) as well as new onset acute kidney injury and light chain cast nephropathy (BMJ Case Rep 2022;15:e246777)

Microscopic (histologic) description

IHC stains for Ig kappa and lambda are used to establish the clonal or polyclonal nature of plasma cells or lymphocytes

Microscopic (histologic) images

Contributed by Kwun Wah Wen, M.D., Ph.D., Julie Guilmette, M.D., Olguta Gologan, M.D. (Case #394) and Miguel Gonzalez-Mancera, M.D.

MALT lymphoma: kappa

MALT lymphoma: lambda

Plasmacytoma: kappa

Plasmacytoma: lambda

Polymorphic light chain expression: kappa

Polymorphic light chain expression: lambda

Immunofluorescence description

Immunofluorescence may be superior to IHC for light chain testing because IHC may cause misdiagnosis due to background staining; however, immunofluorescence requires fresh frozen tissue, which limits its use (Tex Heart Inst J 2012;39:71)

Immunofluorescence images

Contributed by Rajib K. Gupta, M.D., Ramya Krishna Velagapudi, M.D., M.H.A., NephroPath and Ashley Flowers, M.D.

Kidney: kappa positive crystals

Kidney: lambda negative crystals

Kidney biopsy: lambda positive inclusions

Kidney biopsy: kappa negative inclusions

Kappa but not lambda staining of casts

Lambda but not kappa stain of casts

Medullary casts are kappa+, lambda-

Kidney: negative staining for lambda

Kidney: positive GBM and TBM staining for kappa

Restricted lambda positivity, AL amyloid

Restricted kappa positivity, FGN

Restricted kappa positive staining of glomerulus, PGNMID

Restricted kappa
positive staining,
crystalline type
LCPT

Restricted kappa positive staining, LCDD

Positive staining - normal and disease

Kappa and lambda light chains can be detected on plasma cells and to a lesser extent, on B cells, in both nonneoplastic and neoplastic disease
- By immunohistochemistry (frozen section and permanent sections), in situ hybridization, immunofluorescence and by flow cytometry (J Cutan Pathol 2020;47:1103)
- Detection is cytoplasmic or membranous (frozen and permanent sections), cytoplasmic (ISH) but not nuclear
- Enzyme digestion and heat induced epitope retrieval techniques may enhance the performance of IHC staining in low grade B cell lymphoma
As noted above under Uses by pathologists, kappa and lambda testing is useful to differentiate nonneplastic (not kappa or lambda restricted) from neoplastic disease (either kappa or lambda restricted)

Negative staining

Very few cases of immunoglobulin kappa or lambda light chain defects have been reported (Eur J Med Genet 2016;59:219)

Flow cytometry images

Images hosted on other servers:

Prominent monotypic
pattern (lambda, with
minimal kappa)

Molecular / cytogenetics images

Contributed by Genevieve M. Crane, M.D., Ph.D., Leica Microsystems,
Biosystems Division, Ling Zhang, M.D. and Woo Cheal Cho, M.D.

Myeloma: kappa ISH

Myeloma: lambda ISH

Myeloma of marrow with ISH staining

Plasmacytoma, kappa and lambda

LPL, ISH for kappa

LPL, negative lambda ISH

Kappa ISH: not monoclonal

Lambda ISH: not monoclonal

Sample pathology report

Bone marrow aspirate smears, touch imprints, core biopsy and clot section with peripheral smear:
- Plasma cell myeloma (see comment)
- Normocytic anemia, rouleaux formation
- Comment: This 65 year old man recently presented with back pain, anemia and hypercalcemia. Xrays demonstrated lytic bone lesions and serum protein analysis demonstrated an IgG kappa M protein. The bone marrow shows sheets of atypical plasma cells in a hypercellular bone marrow comprising 80% of the intertrabecular space. The plasma cells are CD56+, CD19- and kappa restricted by IHC and flow cytometry.

Board review style question #1

The image above shows kappa light chain restriction in MALT lymphoma. Which of these statements is true?

Immunohistochemistry (IHC) stains cannot establish the polyclonal nature of plasma cells or lymphocytes
In situ hybridization (ISH) for kappa and lambda light chains can establish the clonal nature of plasma cells or lymphocytes
Neoplastic plasma cells usually produce polyclonal light chains
Reactive lymph nodes often produce monoclonal light chains

Board review style answer #1

B. In situ hybridization (ISH) for kappa and lambda light chains can establish the clonal nature of plasma cells or lymphocytes. ISH and IHC can establish the clonal or polyclonal nature of plasma cells or lymphocytes. Answer A is incorrect because IHC stains can establish the polyclonal nature of plasma cells or lymphocytes if both kappa and lambda stains are positive. Answers C and D are incorrect because reactive lymph nodes are typically polyclonal and neoplastic plasma cells usually produce clonal light chains.

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Reference: Kappa & lambda light chains

Board review style question #2

Which of these diseases is typically immunoreactive for kappa or lambda light chains but not both?

Cutaneous lymph node hyperplasia
Diabetic kidney disease
Myeloma
Reactive lymph nodes

Board review style answer #2

C. Myeloma is a clonal (neoplastic) disease that produces either kappa or lambda light chains but not both. Answers A, B and D are incorrect because cutaneous lymph node hyperplasia, diabetic kidney disease and reactive lymph nodes are all polyclonal and produce both kappa and lambda light chains.

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Reference: Kappa & lambda light chains

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