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Case Report | DOI: https://doi.org/10.31579/2640-1053/242
1Associate Professor, Department of Hematology, Bsmmu.
2Medical Officer, Department of Nephrology, Bsmmu.
*Corresponding Author: Rahman F, Associate Professor, Department of Hematology, Bsmmu.
Citation: Rahman F, Mekhola M H, Rahman M S, (2025), Light Chain Disease: A Diagnostic Challenge, J. Cancer Research and Cellular Therapeutics. 9(4); DOI:10.31579/2640-1053/242
Copyright: © 2025, Rahman F. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 01 June 2025 | Accepted: 09 June 2025 | Published: 17 June 2025
Keywords: bone marrow morphology; light chain disease; multiple myeloma (mm); renal impairment
Light-chain multiple myeloma (LCMM) is a rare subtype of multiple myeloma (MM) that can affect various organs, with the kidneys being the most commonly impacted. LCMM typically has a more aggressive progression and is associated with a poorer prognosis. Renal dysfunction in LCMM arises due to the buildup of monoclonal immunoglobulin light chains in the kidneys. In this case, we present a 40-year-old male who came in with generalized swelling, decreased urine output, severe anaemia, and significant renal impairment. He underwent five sessions of haemodialysis and received five units of blood transfusion. Initial screening to exclude plasma cell neoplasm by serum protein electrophoresis showed negative results for monoclonal band. But bone marrow examination revealed an abundance of atypical plasma cells, constituting about 80% of the sample. Immunophenotyping identified 70% clonal plasma cells, with a positive lambda light chain marker. Urine analysis confirmed the presence of free light chains. Quantitative immunofixation markedly higher ratio of involved free light chain (instead of Kappa lambda ratio) but heavy chain level is within normal range. A CT scan indicated subtle changes in the axial and proximal appendicular skeleton. Early diagnosis of LCMM is crucial to initiate timely treatment.
One of the most prevalent hematologic tumours, multiple myeloma (MM) accounts for approximately 1% of all malignancies and is becoming more prevalent worldwide [1-2]. Since MM is diagnosed at an average age of about 65, it is more common in middle-aged and older males [1-4]. Its clinical manifestations include lytic bone lesions, hypercalcemia, anaemia, renal failure, coagulation problems, neurological abnormalities, and an elevatedrisk of infection [1-2,5]. The hallmark of MM is the aberrant growth of clonal plasma cells, which is a malignant condition of B-cells overall [1-2]. In MM, the malignant cells produce abnormalamounts of either monoclonal free light chains, or M-protein, or full immunoglobulins (Ig), which are normally comprised of heavy and light chains and produced by plasma cells [6].
Multiple forms of M-protein exist, but the most commonis immunoglobulin G (IgG), which is followed by immunoglobulin A (IgA)and light-chain-only variants [2-4]. One or more myeloma- defining events, a plasmacytoma in biopsy tissue,and the presenceof 10% or more clonal plasma cells in a bone marrow sample are used to diagnose MM. These include indicators of end-organ damage (like anaemia, renal impairment, hypercalcemia, or lytic bone lesions) or biomarkers of cancer (like bone marrow containing 60% or more clonal plasmacells, changed serum free light chain ratios, or several focal lesions on MRI that are at least 5 mm in size) [7]. About 15% of instances of light-chain multiple myeloma (LCMM),a less frequent subtype of MM,are kidney-related, howeverthey can also affect other organs [2,8]. Because they are unable to form heavy chains, clonal plasma cells in LCMM only make light chains [2]. The hallmark of LCMM is organ damage brought on by aberrantlight chain deposition, regardless of the quantity of light chain synthesis or the load of plasma cells. This results in a worse prognosis and a more aggressive course of the disease [9]. In LCMM, systemic light-chain amyloidosis, bone lesions,and renal failureare frequently seen [2,4]. Similar to MM, autologous stem cell transplantation (ASCT), immunomodulatory medications (like thalidomide and lenalidomide), and proteasome inhibitors (like bortezomib) are commonly used in therapy [8].
A 40-year-old man had been experiencing acute dyspnoea, widespread oedema, and decreased urine production for sevendays. He did not mentionhaving a fever,vomiting, back discomfort, bodily pains, or uncomfortable or frequent urination in the past. Additionally, he did not have a history of high blood pressure or excessive cholesterol. Upon inspection, his blood pressure and body temperature were normal, but he was noticeably pale, short of breath, and much bloated. In addition to no history of organ enlargement or abdominal fluid accumulation, there was no history of blood loss or ongoing bleeding. The results of his neurological, cardiovascular, and musculoskeletal exams were normal.
A high erythrocyte sedimentation rate, raised calcium and phosphate levels, severe anaemia, and acute renal failure were all found during the first examinations (see Table 1). Traces of protein with positive Bence Jones protein were found in a urinalysis, but there were no active sediments. Studies on serum iron were normal. He got five units of blood and three haemodialysis procedures due to acute renal failure. His anaemia was resolved, and his blood creatinine level increased to 5.6 mg/dL. Corticosteroids and hydration were used to treat elevated calcium levels.Electrophoresis of serumproteins was normal.His significant anaemia was submitted to a haematologist for further assessment.
Following a bone marrow aspiration, both normal and atypical plasmacells were found in large quantities (around 80%) (Figure 1). A myeloma panel's immunophenotyping revealed 70% clonal plasma cells with lambda light chain restriction, positive expression of CD38, CD138, CD56, and CD28, negative expression of CD19 and CD45, and no kappa chains (Figure 2).
A free light chain ratio of 0.008:1 was obtained using a serum free light chain test, which showed a much higher lambdalight chain (1398.5mg/L) and a smaller kappalight chain (11.3 mg/L) (see Table 2). Immunofixation revealed good findings for lambda light chains but negative results for heavy chains such as IgG, IgA, and IgM (Figure 3).
Low-grade tracer uptake and mild lytic alterations in the axial and proximal appendicular skeletalsystems were detectedby a PET/CT scan. These results led to the diagnosis of lambda light chain multiple myeloma, even though the serum protein electrophoresis was normal. Following two cycles of the VCD treatment,the patient's serum creatinine level improved to 1.2 mg/dL. With normal serum creatinine levels,he was subsequently moved to the continuing VRD regimen.
The renal biopsywas not performeddue to the involved serum free light chain levelexceeding 1000 mg/L, signifying monoclonal gammopathy of renal significance (MGRS). Following flow cytometry immunophenotyping from a bone marrow sample,which revealed 70% clonal plasma cells with lambda light chain restriction and positive CD38, CD138, CD56, CD28, and cyLambda, but negative CD19 and cyKappa, the patient was ultimately diagnosed with multiple myeloma.
He underwent autologous bone marrow transplantation after achieving complete remission followingsix cycles of the VRD (bortezomib/Velcade, lenalidomide, dexamethasone) protocol and is currently on maintenance treatment.
Figure 1: Bone Marrow Morphology showing plenty of plasma cells
Figure 2: Bone marrow flow cytometry
| Analyte (Unit) | Initial Test Outcome | Reference Standard |
| Hemoglobin (g/dL) | 3.2 | 12.0–16.0 |
| Mean corpuscular volume(fL) | 85.4 | 83–103 |
| Mean corpuscular hemoglobin (pg) | 29.3 | 28–34 |
| Mean corpuscular hemoglobin concentration (g/dL) | 34.3 | 32–36 |
| White blood cells | 12.6 × 103/μL | 4.8–10.8 × 103/μL |
| Neutrophils | 10.3 × 103/μL | 1.8–7.7 × 103/μL |
| Eosinophils | 0.1 × 103/μL | 0.00–0.49 × 103/μL |
| Basophils | 0.0 × 103/μL | 0.0–0.1 × 103/μL |
| Lymphocytes | 1.0 × 103/μL | 1.0–4.8 × 103/μL |
| Monocytes | 1.1 × 103/μL | 0.12–0.80 × 103/μL |
| Platelets | 203 × 103/μL | 150–350 × 103/μL |
| Erythrocyte sedimentation rate (mm/h) | 75 | 0–35 |
| Urea (mg/dL) | 230 | 15–39 |
| Creatinine (mg/dL) | 12.40 | 0.57–1.11 |
| Sodium (mEq/L) | 135 | 135–146 |
| Potassium (mEq/L) | 4.79 | 3.5–5.1 |
| Phosphorus (mg/dL) | 7.0 | 2.5–4.9 |
| Albumin (g/dL) | 4.1 | 3.4–5.0 |
| Serum calcium | 13.7 mg/dl | 8.5-10.5 /dl |
| Iron studies | ||
| Serum iron (g/dL) | 9 | 50–170 |
| Total iron binding capacity (g/dL) | 241 | 250–450 |
| Serum ferritin (ng/mL) | 152 | 8–252 |
| Urine routine microscopic examination | ||
| Protein | Trace | Nil |
| Bence jones protein | Present | Absent |
| Red blood cell(RBC) | 0-3 | 0-5 |
| White blood cell(WBC) | 3-5 | Nil |
| Cast | Nil | Nil |
Table 1: Preliminary laboratory tests
| Test | Result | Reference value |
| KappaLight Chain | 11.3 mg/L | 200-440 mg/dl |
| LamdaLight Chain | 1398.5 mg/L | 110-240 mg/dl |
| Kappa:Lamda | 0.008:1 | 0.31-1.56 |
Table 2: The serum free light chain assay
An uncommon hematologic condition, LCMM (Light Chain Multiple Myeloma) makes up 15% of all instances of multiple myeloma (MM)2. Information for a thorough case report on LCMMis scarce in the existingliterature. The deposition of monoclonal immunoglobulin light chains in different organs is what defines it [10]. Depending on which organs are impacted, LCMM might present with different clinical symptoms [11].
The clinical features of LCMM are similar to other forms of MM, with bone pain and kidney impairment being the most common presenting symptoms. Over the course of the disease, patients may also develop lytic bone lesions, hypercalcemia, anaemia, pleural effusion, and extramedullary involvement [2,4]. In cases where the kidneys are involved, monoclonal light chains produced by clonal plasma cells in the bone marrow are deposited in the glomeruli, leading to characteristic nodular glomerulosclerosis [12]. A hallmark feature of LCMM is the absence of complete clonal immunoglobulin production by malignant plasma cells [2]. This is important because the absence of an M-spikein serum electrophoresis can lead to misdiagnosis. Therefore, evaluating serum and urine free light chains is critical when LCMM is clinically suspected.
Patients with LCMM are more likely to have renal involvement than those with other types of MM [2,4]. Significant morbidity, a worse overall survival rate, and increased rates of early mortality have all been linked to renalimpairment at diagnosis in LCMM [13-15]. Supportive care and the timely start of antimyeloma medication are the cornerstones of treatment for LCMM with renal insufficiency [16]. For LCMM with renal impairment, boratezolomib-based regimens are the recommended course of therapy [13-16], since they have been shown to be more effective than alternative approaches [2,4].
In our case,a 40-year-old man presented with generalized swelling(anasarca), severe anaemia, hypercalcemia, and severe renal insufficiency. Our initial diagnosis focused on MM. Serum protein electrophoresis showed a flattened gamma zone with no visible M-spike. A bone marrow study confirmed the diagnosis of kappa LCMM.The patient was immediately referred to a haematologist for prompt initiation of treatment.
The hallmark of LCMM, a rare kind of multiple myeloma (MM), is the absence of full clonal immunoglobulin production by the cancerous plasma cells. Serum protein electrophoresis in LCMM typicallydoes not show an M-spike.Patients presenting with symptoms suggestive of MM, such as anaemia and renal impairment, should be carefullyevaluated during assessment. Since LCMM has a worse prognosis than more commonforms of MM, early identification and prompt initiation of treatment are crucial for improving patient outcomes.
Each author provided valuable input during the article's development and critical editing for noteworthy intellectual content, and they all approved the final version.
All authors declaredthat they have no conflict of interest regarding this publication.
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