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Several previous case reports have shown that patients with immunoglobulin D (IgD) multiple myeloma (MM) can be withdrawn from hemodialysis, however, the characteristics that can predict withdrawal in these patients have not yet been elucidated. A 57-year-old Japanese woman required hemodialysis because of renal dysfunction due to IgD-λ and Bence Jones protein-λ MM. Bortezomib-based chemotherapy nine days after admission led to her withdrawal from hemodialysis on Day 50. In our case-based review, younger age and early initiation of bortezomib-based chemotherapy emerged as possible predictors of successful hemodialysis withdrawal.

BACKGROUND: We report a case of a patient with immunoglobulin A multiple myeloma associated with a masked kappa light chain. Serum immunofixation showed a monoclonal band in the IgA heavy chain lane without corre-spondence with the light chain and a monoclonal band in total kappa light chain lane without correspondence with the heavy chain.
METHODS: To distinguish between heavy chain disease and immunoglobulin with \"masked\" light chains, two tubes containing the patient\'s serum were incubated with a very high concentration of anti-total kappa and anti-total lambda antisera for 48 hours at 4°C in order to facilitate immunoprecipitation of the involved light chain. After centrifugation, the supernatant was analyzed by using the IFs method on the Hydrasys 2 Scan Focusing Sebia® without dilution. Then we applied the anti-IgA, anti-total kappa and anti-total lambda antisera.
RESULTS: The serum immunofixation test of the sample treated with a high concentration of anti-total kappa showed the disappearance of the monoclonal bands corresponding to IgA heavy chain lane and kappa light chain lane, indicating that precipitation had occurred and that the IgA did have kappa light chains that could not be detected by the standard immunofixation protocol. The serum immunofixation test of the sample treated with anti-total lambda showed the disappearance of the polyclonal background in lambda light chain lane, confirming that the precipitation with lambda light chains according to the previously mentioned protocol has done well.
CONCLUSIONS: This case illustrates some of the difficulties encountered and the corrective actions that can be taken for the detection of immunoglobulins with masked light chains.

Typically, myeloma cells express a monoclonal immunoglobulin (Ig), either heavy or light chain. Here, we present a case of multiple myeloma with clonal dual expression of kappa and lambda light chain in a 74-year-old woman. Awareness of rare biphenotypic myeloma is important for proper diagnostic workup. A 74-year-old woman underwent hip replacement with an incidental finding of 20% plasma cells in the femoral head. Subsequent bone marrow biopsy also showed about 30% of plasma cells negative for CD20, CD56, and CD117. Immunohistochemistry (IHC) and in situ hybridization studies showed a mixture of kappa and lambda plasma cells. Flow cytometry showed ambiguous results for cytoplasmic Ig light chains kappa and lambda. However, cyclin D1 was highly expressed by plasma cells, and increased free kappa light chains were identified in serum. Further investigation by double IHC demonstrated co-expression of kappa and lambda light chains in the same cells. Fluoresces in situ hybridization studies were positive for t(11;14)(q13;q32) and the deletion 13q. Since its first description by Taylor and Burns in 1974, the demonstration of restricted cytoplasmic Ig light chain expression by immunohistochemistry is 1 of the basic tools for corroborating clonality of the plasma cells in tissue biopsy. IHC results in myeloma with dual expression of Ig light chains may suggest polyclonal plasma cell population, especially when plasma cells do not form sheets in the bone marrow. In an appropriate clinical setting, other investigations are needed to exclude plasma cell neoplasm, even with seemingly \"polytypic\" results by IHC.

A woman in her 70s with vague gastrointestinal (GI) symptoms and unintentional weight loss was referred to endoscopy clinic for investigation and consideration of GI malignancy. CT of the thorax, abdomen and pelvis showed a suspicious mass in the oesophago-gastric junction with a lytic lesion on S1-S2 sacrum. A subsequent upper GI endoscopy revealed two raised, ulcerated tumours on the lesser curvature of the stomach. By the time an MRI of the whole spine was done which revealed multiple metastases involving thoracic, lumbar and sacral skeleton, she had developed leg weakness and paraesthesias, consistent with the imaging findings. A positron emission tomography/CT scan further confirmed the above findings. The initial working diagnosis was primary GI tumour with bony metastases. However, she was later referred to the haematology team after the immunohistochemistry of the tumour showed that it was of a plasma cell origin (CD138 positive) associated with lambda light chain deposits. Serum-free light chain showed a raised lambda light chain of 272 mg/L and kappa light chain of 11.3 mg/L and involved/uninvolved light chain ratio of 24. Bone marrow biopsy confirmed a plasma cell myeloma with moderate disease burden. Monoclonal lambda chains were demonstrated on immunofixation but negative on serum protein electrophoresis and hence a diagnosis of oligosecretory myeloma with GI involvement was made. Subsequent management involved physiotherapy, pain management and chemotherapy, where this woman was commenced on Velcade (generically known as bortezomib), thalidomide and dexamethasone and she continued to experience clinical and biochemical improvement.

OBJECTIVE: Amyloidosis is a systemic or localized disease of protein deposition characterized by amorphous eosinophilic morphology and positivity of Congo Red staining. The typing of amyloidosis is becoming increasingly important because therapeutic agents for each amyloidosis type have been developed. Herein, the authors review the autopsy cases at an institution to reveal the putative Japanese characteristics of each amyloidosis type and evaluate the clinicopathological significance of each type.
METHODS: A total of 131 autopsy cases of systemic and localized amyloidosis were retrieved for classification by immunohistochemistry. Immunohistochemistry for transthyretin, amyloid A (AA), immunoglobulin light-chain kappa and lambda, and β2-microglobulin was performed for all cases.
RESULTS: The 131 amyloidosis cases were classified as follows: 71 cases (54.2%) of transthyretin amyloidosis, 32 cases (24.4%) of AA amyloidosis, 8 cases (6.1%) of light-chain amyloidosis, and 5 cases (3.8%) of β2-microglobulin amyloidosis, along with 15 equivocal cases (11.5%). All cases showed myocardial involvement of amyloidosis. Histopathologically, the transthyretin type was significantly associated with the interstitial and nodular patterns, and with the absence of the perivascular and endocardial patterns. The AA type was significantly associated with the perivascular and endocardial patterns, and with the absence of the nodular pattern.
CONCLUSIONS: The authors revealed the putative characteristics of cardiac amyloidosis in Japan by using autopsy cases. About 90% of amyloidosis cases were successfully classified using only commercially available antibodies.

Tick-borne encephalitis (TBE) is an acute disease caused by the tick-borne encephalitis virus. Due to the viral nature of the condition, there is no effective causal treatment for full-blown disease. Current and nonspecific TBE treatments only relieve symptoms. Unfortunately, the first phase of TBE is characterized by flu-like symptoms, making diagnosis difficult during this period. The second phase is referred to as the neurological phase as it involves structures in the central nervous system-most commonly the meninges and, in more severe cases, the brain and the spinal cord. Therefore, it is important that early markers of TBE that will guide clinical decision-making and the choice of treatment are established. In this review, we performed an extensive search of literature reports relevant to biomarkers associated with TBE using the MEDLINE/PubMed database. We observed that apart from routinely determined specific immunoglobulins, free light chains may also be useful in the evaluation of intrathecal synthesis in the central nervous system (CNS) during TBEV infection. Moreover, selected metalloproteinases, chemokines, or cytokines appear to play an important role in the pathogenesis of TBE as a consequence of inflammatory reactions and recruitment of white blood cells into the CNS. Furthermore, we reported promising findings on tau protein or Toll-like receptors. It was also observed that some people may be predisposed to TBE. Therefore, to understand the role of selected tick-borne encephalitis biomarkers, we categorized these factors and discussed their potential application in the diagnosis, prognosis, monitoring, or management of TBE.

IgG4-related disease (IgG4-RD) is a newly classified but poorly understood immune-medicated systemic disease. It causes potential fibroinflammation in one or more organs, characterized by tumescent organs and marked IgG4-positive plasma cells infiltration in the affected tissues. There have been a few cases revealing close relationship between IgG4-RD and formation of B cell lymphoma. Diffuse large B cell lymphoma (DLBCL) and extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissue are the most common sub-types ever described, whereas the exact mechanism remain unclear.
We report a 64-year old Chinese male who presented chronic kidney disease and was initially diagnosed typical IgG4-RD. Pathological findings revealed there was restricted expression of lambda light chain in the kidney. There was also elevated uptake abnormality observed in 18F-FDG-PET/CT. Prednisone combined with oral cyclophosphamide helped the patient to get a partial remission of renal function and an obvious decrease of IgG4 level. However, he developed DLBCL 16 months after IgG4-RD diagnosis. The DLBCL is speculated to transform from a pre-existing but possible missed diagnosed EMZL.
Concurrent IgG4-RD with kidney-origin EMZL developing DLBCL has never been reported in the literature. Clinicians should keep in mind that lymphoma may occur in IgG4-RD. The mechanism of lymphomagenesis potential in IgG4-RD needs further study.

Belimumab (Benlysta®) is a human immunoglobulin G1λ monoclonal antibody that inhibits the binding of soluble B lymphocyte stimulator to B cells. It is the only biological agent currently approved for the treatment of non-renal systemic lupus erythematosus (SLE). Belimumab is approved in the EU, the USA and other countries as add-on therapy in adult patients with active, autoantibody-positive SLE despite standard therapy. In phase III trials, treatment with IV or SC belimumab plus standard therapy was effective in terms of reducing overall disease activity and reducing the incidence and severity of flares, without worsening of patients\' overall condition or the development of significant disease activity in new organ systems. Sustained disease control was maintained during longer-term (up to 10 years) treatment with IV belimumab. Belimumab also demonstrated steroid-sparing effects and was associated with clinically meaningful improvements in health-related quality of life and fatigue. Belimumab was generally well tolerated in clinical trials, with low rates of immunogenicity. In view of the flexibility regarding the route of administration and the convenience of the once-weekly, self-administered, SC regimen, add-on therapy with belimumab is a useful treatment option for patients with active, autoantibody-positive SLE despite standard therapy.

BACKGROUND: Light chain deposition disease (LCDD) is a monoclonal immunoglobulin deposition disease (MIDD) that is characterized by the deposition of monoclonal light chains in multiple organs, including the kidney. It is a rare disorder caused by an underlying monoclonal plasma cell dyscrasia. LCDD with renal involvement causes proteinuria, which sometimes can lead to nephrotic syndrome. The monoclonal light chains are mostly in the κ form. Treatment of LCDD is the same as that for multiple myeloma (MM); however, some conventional anticancer drugs show substantial toxicity and therefore cannot be administered to older patients or those with renal impairment.
METHODS: An 80-year-old woman was referred to our department with severe nephrotic syndrome (13.6 g/gCr) and anemia. A renal biopsy showed mesangial proliferation and mesangial matrix expansion, and immunohistochemistry showed positive staining for λ chains along the glomerular basement membrane, but was negative for κ chains or amyloid deposition. A bone marrow biopsy revealed 64% plasma cells. Immunoglobulin G (IgG)-λ type M protein was detected, and the levels of free λ chain was significantly increased. We concluded that her nephrotic syndrome was caused by LCDD, which resulted from IgG-λ MM. The induction of a BCD (bortezomib, cyclophosphamide, and dexamethasone) treatment regimen did not lead to a hematological response or decrease in proteinuria. The administration of combination therapy of lenalidomide and prednisolone led to the successful reduction of proteinuria and hematuria.
CONCLUSIONS: We presented a very rare case report describing the successful treatment of LCDD (λ chain)-induced nephrotic syndrome with lenalidomide.
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