Case Report: Management of Primary Tracheobronchial Light Chain Amyloidosis in a Patient With Biclonal Gammopathy Using a Systemic Bortezomib-Based Regimen

Primary tracheobronchial light chain (AL) amyloidosis is a rare and heterogeneous disease characterized by the buildup of amyloid deposits in the airway mucosa. Although its treatment remains challenging, the current view is that the localized form can be treated conservatively due to its slow progression. While radiotherapy has proven effective in treating localized form of the disease, some patients do not respond to local treatment and continue to experience poor quality of life, highlighting the need to explore additional treatment strategies. In this report, we discuss a case of primary tracheobronchial AL amyloidosis with biclonal gammopathy (IgA κ and IgG κ) in a 46-year-old man who was transferred to our hospital due to dyspnea progression over the preceding 3 years. Chest computed tomography revealed irregular tracheobronchial stenosis with wall thickening, and histological examination of the bronchial biopsies confirmed the diagnosis of endobronchial AL amyloidosis. Owing to the poor effect of radiation therapy and treatments for improving airway patency, he was treated with a systemic chemotherapy regimen [cyclophosphamide-bortezomib-dexamethasone (CyBorD)]. We observed substantial improvements in his dyspnea, highlighting the potential of systemic therapy to improve quality of life of patients with tracheobronchial AL amyloidosis. However, the long-term pathological changes associated with local bronchial lesions require further investigation.

Biclonal Multiple Myeloma- A Case Series

Multiple myeloma is a prototype of plasma cell dyscrasias characterized by monoclonal abnormal proliferation of immunoglobulin secreting plasma cell in the bone marrow ; resulting in production of monoclonal (M) protein (IgG,IgA,IgM,IgD) and or light chain concentrations (kappa or lamda) identified by protein electrophoresis and or immunofixation of serum or urine. The term biclonal multiple myeloma are defined by coexistence of two different M components, which could be either from a single clone or two separate clones producing two distinct bands in electrophoresis and or immunofixation of serum or urine. Biclonal gammopathy is a rare entity with upto 1% of newly diagnosed case of multiple myeloma have two M component in serum immunofixation electrophoresis. Here we share our experience of four cases of biclonal myeloma successfully diagnosed and treated with standard chemotherapy with satisfactory clinical outcome from a single tertiary care centre.

EXPRESS: The effect of paraprotein polymerisation on quantitation by capillary zone electrophoresis and Hevylite®

Objectives Up to 3% of patients with monoclonal gammopathies have multiple serum paraproteins. This article investigates whether multiple isotype-matched paraproteins, as seen on capillary zone electrophoresis (CZE), are truly biclonal. Methods Sera containing multiple isotype-matched paraproteins were treated with the reducing agent dithiothreitol (DTT) and CZE performed pre- and post-treatment. Band resolution and effect of resolution on quantitation of paraprotein burden was assessed. The Hevylite® turbidimetric assay was also evaluated for ability to quantify such paraproteins. Results Among patients with biclonal isotype-matched (BIM) paraproteins, 23/24 (96%) IgA paraproteins resolved into a single band following treatment with DTT compared with only 1/12 (8%) IgG paraproteins. Daratumumab therapy accounted for the second band in 5/9 non-resolving IgGκ paraproteins. Where initially quantified as a single IgA “complex” (multiple bands in close proximity), the single post-DTT band averaged 2.8 g/L less (P=<0.001), likely due to inclusion of lower amounts of underlying serum proteins (y=0.97x-2.03, R2=0.993). Quantitating IgA BIM (n=58) using the Hevylite® assay gave higher results (P=0.002) than CZE (y=1.48x–7.13, R2=0.959). In contrast, single IgA paraprotein results (n=48) did not differ between the two methods (P=0.466; y=1.24x – 2.74, R2=0.898), suggesting that polymerisation enhances Hevylite® quantitation. Conclusions These results suggest that disulphide-mediated polymerisation of IgA paraproteins is more common than true biclonal gammopathy and support DTT treatment of samples with isotype-matched IgA bands before quantifying by CZE. The Hevylite® assay should be utilised with caution where polymerisation is likely. Where IgGκ BIM paraproteins appear on CZE, Daratumumab therapy should be considered.

A Rare Presentation of Biclonal Gammopathy in Multiple Myeloma with Simultaneous Extramedullary Involvement: A Case Report

Multiple myeloma is characterized by an abnormal clone of plasma cell infiltration in the bone marrow and presence of a high level monoclonal immunoglobulin (M-protein) in the serum or urine in most cases. The monoclonal protein is usually detected as a discrete band in the gamma globulin region by serum protein electrophoresis. Rarely, it may show a simultaneous presence of two distinct bands, which could be either from a single clone, or two separate clones. We report a very unusual presentation of biclonality with lambda restricted IgG predominant cells from cervical lymph node and kappa restricted IgA cells from the bone marrow simultaneously.

Demystifying Biclonal Gammopathy: A Pathologist’s Perspective

Background The production of 2 monoclonal proteins characterizes biclonal gammopathic manifestations (BGMs). The available medical literature from India is chiefly restricted to case reports. Objective To study the incidence of BGMs in a tertiary care center in Chandigarh, India, during a 4-year period. We evaluated these cases further for their laboratory characteristics. Methods We scrutinized the contents of a database containing information from the studied 4-year period. Cases reported as BGMs on serum protein electrophoresis (SPEP) and confirmed by serum immunofixation electrophoresis (SIFE) were included. Results A total of 15 cases, from a cohort of 914 cases of monoclonal gammopathic manifestations (MGMs), were available. On SPEP, 2 M bands were observed in 12 cases. On SIFE, 4 cases were reported as being of true BGMs. The most common heavy-chain combination observed was immunoglobulin (Ig)A-IgG. Follow-up was available in 2 patients. Conclusion Identification of BGMs increases diagnostic precision, despite that the treatment is similar to that for monoclonal gammopathic manifestations (MGMs). BGMs can be transitory and may be observed at presentation or during the disease course.