Clinical diagnosis
Case 148
【Progress】
The following laboratory test revealed deterioration of renal disorder and progressive anemia. Then, she was transported to the hospital where the more expertise treatment from hematology department was possible.
【Discussion】
Multiple myeloma originates from plasma cells which produce immunoglobulin (Ig) such as IgM, IgG, IgA, IgE and IgD. IgM is the largest in size of the immunoglobulins and functions at the initiation of immune system. IgM with complement C1 proceeds the opsonization of antigens by leukocytes and cytolysis. IgM is mainly responsible for agglutination of the blood in case of mistaken blood type transfusion. IgA plays a main role of immune system of mucosal membranes against microorganism invasion from gastrointestinal tract, respiratory tract, salivary tract and reproductive tract. IgA is secreted 3 to 5 g/day from mucous membrane which is up to 15% of total globulin produced throughout body (1-4). IgA is found in small volume in blood. Meanwhile, IgG represents approximately 75% of serum antibodies (1). IgG play a crucial role against microorganism invading to blood.
Plasma cells originate from B cells. When B cells respond to an infection,
they mature and change into plasma cells with assistance of helper T cells. A cancer of plasma cells which abnormally produce IgG, IgA, IgD or IgE is called multiple myeloma and a cancer of plasma cells which abnormally produces IgM is called primary macroglobulinemia. As related diseases to multiple myeloma, primary macroglobulinemia, solitary plasmacytoma and light chain amyloidosis are listed. Myeloma secrets M (myeloma) protein with no function which is found in blood and urine, and substances to activate bone destruction of osteoclasts and repress osteogenesis of osteoblasts. Destruction of bone results in pathological fracture and hypercalcemia. The massive increase of M protein results in lowering of normal immune globulin being susceptible to infection and results in hyper-viscosity syndrome, renal disorder and amyloidosis (5). In our case, abnormal high value of IgA in blood was detected and destruction of lumbar vertebra was shown on CT and MRI.
Because the incidence of metastatic bone tumor or multiple myeloma occurs with advance of age, it is clinically important to differentiate between them. However, both metastatic bone tumor or multiple myeloma appear as osteolytic lesions, indicative of difficulty of differential diagnosis. The latest study of MRI on the differentiation said the average of ADC was 0.75 mm2/sec versus 1.081 mm2/sec in multiple myeloma vs metastatic tumor and the cutoff values of ADCav, was 0.956 mm2/sec (sensitivity 97%, specificity 61%)(6, 7). In our case, MRI and CT showed space multiple occupying lesions on thoracic and lumbar vertebrae. Regrettably, diffusion weighted image and ADC values were not performed in our case.
【Summary】
We present a sixty nine year-old female suffering from severe lumbago. CT and MRI showed multiple space occupying lesions, hardly differentiating multiple myeloma from metastatic bone tumors. Laboratory test revealed eGFR 21.7 ml/min/1.73m2, CRP 2.18 mg/dL, and IgA 2426 mg/dL, indicating a diagnosis of multiple myeloma. It is borne in mind that multiple myeloma is a cancer of plasma cells. Following micro-organism infection, plasma cells differentiate and mature from B cells with assistant of helper T cells. Plasma cells produce IgM, IgG, IgA, IgE and IgD, while multiple myeloma secrets M protein and substances to activate osteoclasts and repress osteoblasts, inducing pathological fracture and hypercalcemia. The massive increase of M protein results in lowering of normal immune globulin being susceptible to infection and results in hyper-viscosity syndrome and renal disorder. The latest study of MRI revealed the average of ADC was lower in multiple myeloma than metastatic bone tumor the cutoff values of ADCav, was 0.956 mm2/sec (sensitivity 97%, specificity 61%).
【References】
1.Immunoglobulin G from Wikipedia
2.Bonner A, et al. "Location of secretory component on the Fc edge of dimeric IgA1 reveals insight into the role of secretory IgA1 in mucosal immunity". Mucosal Immunology. 2009; 2 : 74–84.
3.Brandtzaeg P, et al. "Let's go mucosal: communication on slippery ground". Trends in Immunology. 2004; 25 : 570–7.
4.Macpherson AJ, et al. "The functional interactions of commensal bacteria with intestinal secretory IgA". Current Opinion in Gastroenterology. 2007; 23 : 673–8.
5.Papadopoulou, EC, et al. Multiple myeloma and bone disease: pathogenesis and current therapeutic approaches. Hippokratia. 2010 Apr-Jun; 14(2): 76–81
6.Horger M, et al. Whole-body diffusion-weighted MRI with apparent diffusion coefficient mapping for early response monitoring in multiple myeloma: preliminary results. AJR Am J Roentgenol 2011;196(6):W790–795.
7.Giles SL, et al. Assessing myeloma bone disease with whole-body diffusion-weighted imaging: comparison with x-ray skeletal survey by region and relationship with laboratory estimates of disease burden. Clin Radiol 2015;70(6):614–621.
2019.6.12