Multıple Myeloma wıth Homogenous Secretıon of Lambda Lıght Chaın Immunoglobulın: A Case Report

About 20% of people with multiple myeloma (MM) produce only light kappa chains which is produced in 80% of cases. This population of MM patients may be missed where the laboratory could not effectively detect free light chains of immunoglobulins as it is identification and quantitation should be carried out in all cases of suspected MM; especially in those with no monoclonal bands on serum protein electrophoresis and or immunofixation.


INTRODUCTION
Multiple myeloma (MM) is a neoplastic plasma cell disorder that is characterized by clonal proliferation of malignant plasma cells in the bone marrow microenvironment. The malignant plasma cells produce excessive monoclonal (M) proteins which includes; IgG 52%, IgA 21%, Light chain 16%, Biclonal 2% and IgM 0.5%; the IgD and IgE types are very rare. On the other hand, 3% of MM patients have non-secretory myeloma [1].
Patients with light chain myeloma are more prone to developing renal failure. This monoclonal light chains may be deposited in multiple organs to form light-chain deposition disease (LCDD). LCDD is a rare disease characterized by deposition of non-amyloid immunoglobulin light chains, and they do not stain with Congo red and do not exhibit a fibrillar structure when examined ultrastructurally [2][3][4]. It is categorized as a "monoclonal deposition disease" in the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues [5]. LCDD was first described in 1976 in two patients with end-stage renal disease as granular deposits of free light chains in multiple organs, including the kidneys, that did not stain with Congo red [6]. A single clone of plasma cells is responsible for overproduction of kappa chains and, very rarely, lambda chains [7]. A monoclonal population of plasma cells can be detected in the bone marrow, and an altered serum-free light chain ratio is present [8]. In 25% of patients, an abnormal serum free light chain ratio is noted, even without an abnormal finding with serum and or urine electrophoresis with immunofixation [9]. LCDD should also be excluded in patients who have both renal disease and a lymphoplasmacytic disorder like macroglobulinaemia, lymphoma and chronic lymphocytic leukemia capable of producing monoclonal light chains [4].
LCDD is noted to be a disease of adults (median age 56 years, range 33-39 years which occur in association with either myeloma in 65% of cases or monoclonal gammopathy of undetermined significance(MGUS) [10,11]. There is no evidence of sex discrimination neither is there evidence of ethnicity effect [10,11].
We hereby present this rare case of lambda light chain MM, diagnosed in our facility for the first time whereby most of the biochemical tests were normal to underscore the importance of complete immunoglobulin analysis, including FLC. Prompt bone marrow examination in every suspected case of MM should be done even in those with no monoclonal bands on serum protein electrophoresis and or immunofixation.

CASE REPORT
The 64 year old poultry farmer was referred to Haematology department by the neurosurgeons with a positive BJP result. He had presented to them with complaints of progressively worsened inability to walk following a fall from a height on a ladder, even though he had previously experienced a prolonged low intensity waist pains. There was associated urinary urgency, occasional urge incontinence and constipation. The review of other systems were not remarkable. There was no past history of blood transfusion.
Physical examination essentially revealed chronically ill-looking man with mild pallor, normal vital signs and there was no pedal edema or lymphadenopathy. The central nervous system examination revealed sensory level of T6/T7, hyperaesthesia at T12/L1 bilaterally, reduced power of 3-4 and brisk deep tendon reflexes of lower limbs. The anal sphincter was lax. However, the examination of the respiratory, cardiovascular and gastrointestinal systems revealed no abnormal findings.
Serum protein electrophoresis revealed a thin discrete band in the gamma globulin region. The total protein was 6.3 g/dl (normal = 6-8 g/dl), Albumin-4. Plain cervical spine X-ray showed minimal anterior marginal osteophytes in C4 and C5 vertebrae in keeping with early cervical spondylosis while lumbosacral spine x-ray showed decreased height of L4 and straightened lumbosacral spine. Chest X-ray revealed only unfolded aorta.
Spine magnetic resonance imaging (MRI) confirmed cervical spondylosis with multiple disc bulges at C3/4, C4/5 and C5/6 , thickened ligamentum flavum course at C4-C6, soft tissue swelling at cervico-thoracic junction posterior to the spine, osteolytic lesionns of T1 with theca and cord compression and soft tissue swelling obliterating the spinal cord behind T4. The lumbosacral spine showed osteolytic lesions at L3 and L4, and cord compression at L3/L4. Based on the MRI findings of multi-level cord compression, the patient had a decompression laminectomy and bone marrow specimen for histology revealed nodular aggregate of malignant plasma cells with extensive bone destruction. A bone marrow aspiration cytology, carried out thereafter, revealed depression of the erythroid and myeloid cell lines with marked increase in plasma cells and plasmablasts constituting 70% and 10% of the bone marrow nucleated elements respectively.

. Level of immunoparesis at diagnosis
Patient was diagnosed as a case of lambda light chain multiple myeloma and was commenced on combination therapy comprising mephalan, thalidomide and prednisolone and this later changed to bortezomib, dexamethasone and thalidomide (VTD) after 2 cycles of the former.
The lower limb power has improved to grade 5 and he is currently ambulating without support after 5 cycles of VTD. The lambda light chain has reduced to 477 mg/dl from 4,715 mg/dl at diagnosis and his renal profile remain normal (Figs. 2 and 3).

DISCUSSION
Multiple myeloma (MM) is a malignant neoplasm of the plasma cells [11]. The malignant cells arise from post-germinal center of lymph nodes and home back to the bone marrow [12,13].
MM was first documented in 1844 [14]. The annual incidence is 4 per 100 000 and it represents approximately 1% of all malignancies, 10% of all haematological malignancies and second most common after non Non-Hodgkin's lymphoma [15,16]. MM has been reported to be twice commoner in blacks than in white and has a M: F of 1.4:1 [17]. The median age at diagnosis is 65-70 years and only 15% and 2% of the patients are younger than 50 and 40 years respectively [1].
Aside from elevated free light chain of 4,715 mg/dl (normal range: 5-71-26.3) and severely low reduced kappa:lambda ratio of <0.01 (normal range: 0-26-1.65); other main findings include anaemia, moderately raised ESR of 54 mm in 1 st hr, immunoparesis and abnormal plasmacytosis in bone marrow aspiration cytology as well as the marrow sample at decompression laminectomy sent for histology (Fig. 1). However, we found normal renal profile and normal calcium and phosphate levels. This is of importance because hypercalcaemia often occur in MM and renal impairment is frequently expected in lambda-type LCDD.
The presence of only a light chain monoclonal protein is seen in approximately 20% of MM cases, more often kappa light chain (in 80%) and the condition is known as light chain myeloma [18]. In this index case, amyloid light-chain (AL)amyloidosis consisting predominantly of lambda light chains is expected but kappa light chains are predominantly involved in LCDD. Electron microscopy is known to be helpful in distinguishing between these two lesions.
The diagnosis of light chain disease depends on the availability of specific antisera against the five known classes of immunoglobulins and against free and bound light chains. In MM, there is increased concentration of monoclonal protein, which is an abnormal immunoglobulin produced by the malignant plasma cells, along with normal or reduced concentration of other normal immunoglobulins.
In the analysis of serum protein electrophoretic pattern reported locally [19] in the 19 cases of MM in a five year review, non-secretory MM was found in 16%. These so called "non-secretory" may include undiagnosed light chain myeloma because of the unavailability of specific antisera for the free light chains in plasma or in urine at the time of diagnosis.
Determination of SFLC ratio is important not only for diagnosis, it is also important for the monitoring of the disease. It is a very sensitive indicator in the evaluation of early response and also of early relapse. Its determination also gives valuable information on MGUS.
Plasma cell neoplasms secreting only kappa or lambda light chains were not previously diagnosed in our facility even though we received and treated an average of 4.2 cases of MM per year[19].

CONCLUSION
This case report highlights the fact that light chain myeloma might have been previously overlooked because of poor awareness and the non-availability of required monoclonal antisera against light chains of immunoglobulins. It has also shown that diverse variation of MM exists even in our environment and that a wellequipped laboratory capable of providing all necessary monoclonal antibodies to analyze immunoglobulin subtypes in each of our facilities will improve diagnostic accuracy and proper prognostication of our MM cases.

CONSENT
All authors declare that 'written informed consent was obtained from the patient for publication of this paper and accompanying images.

ETHICAL APPROVAL
It is not applicable.