Four months prior to admission this 81-year-old woman had a vertebral compression fracture that was treated with vertebroplasty at an outside hospital. One month later she had a second vertebral compression fracture, which was again treated with vertebroplasty. An extensive radiologic workup performed at that time had negative findings. The patient's past medical history included a 17-year history of type 2 diabetes mellitus, breast cancer treated with a right radical mastectomy 5 years prior to admission (negative follow-up), hyperlipidemia, and osteoporosis. She was referred to this hospital for evaluation and treatment of renal failure.
On admission, her physical exam revealed only limitation of back movement and “jabbing” leg pains with passive movement. Initial laboratory data included a serum creatinine level of 3.0 mg/dL (265.2 μmol/L), a 24-hour urine protein level of 0.562 g/dL (5.62 g/L), and hemoglobin level of 0.99 g/dL (9.9 g/L). The patient's evaluation included a renal ultrasound study, which returned normal results, and a skeletal survey, which showed multiple vertebral compression fractures. Additional laboratory studies included serum protein electrophoresis, which showed 2 monoclonal bands in the gamma region (Figure 1), and the immunofixation studies shown in Figures 2 and 3. In Figure 2, 2 monoclonal bands are present in both the serum protein (SP) and λ light chain lanes. Monoclonal bands were not visualized in the immunoglobulin (Ig) G, IgA, IgM, or κ light chain lanes. In Figure 3, the 2 monoclonal bands are again present in the serum protein and λ lanes, and additional single monoclonal bands are present in the IgD and free λ light chain lanes. The bone marrow exam showed hypercellularity, decreased erythropoiesis, decreased granulopoiesis, decreased megakaryopoiesis, and 71% abnormal plasma cells (Figure 4). There was no evidence of metastatic adenocarcinoma.
What is your diagnosis?
Pathologic Diagnosis: Multiple Myeloma With a Monoclonal Serum IgD λ Immunoglobulin
It is important to identify IgD multiple myeloma because the prognosis for this disease is worse than for other forms of myeloma.1 Expected length of survival for this disease has been reported to vary from 12 to 17 months.2 The most common causes of death are renal failure, cardiopulmonary complications, and infections.3
Immunoglobulin D myeloma is relatively rare, representing less than 1% of all myelomas. Immunoglobulin D myeloma was first described by Rowe and Fahey in 1965, according to Bladè and Kyle.2 Immunoglobulin D multiple myeloma is more common in men4 and has a mean age of presentation between 55 and 60 years,1 whereas other myelomas present at a mean age of 62.2 Presenting features in IgD myeloma include bone pain in 72%,1 fatigue in 36%, weight loss in 32%, extramedullary plasmacytomas in 19%, and amyloidosis in 19% of patients.5 Another unusual feature of IgD myeloma is that patients with IgD myeloma are less likely to have an M-spike than are patients with other types of myeloma (only 60% of cases have one).2 The M-spike, if present, is likely to be less than 2000 mg/dL (20 g/L).2 In fact, IgD myeloma will often present with a protein electrophoretic pattern showing a normal or even a hypogammaglobulinemia pattern.5
Although most patients with multiple myeloma (60% of cases) have κ light chains, in IgD myeloma the light chain is λ.2 Light chain proteinuria is seen more frequently than in other types of myeloma, which, combined with the disease's tendency to have no M-spikes, makes it similar to Bence Jones myeloma.2 This light chain proteinuria correlates well with an elevated incidence of renal failure in IgD myeloma,2 with azotemia occurring in 70% of patients with IgD myeloma.3 Other unique features of IgD myeloma include a 10% incidence of enlarged lymph nodes and increased association with amyloidosis. Extraosseous involvement6 has been reported to occur in 19% to 65% of cases in various studies.
It has been suggested that the malignant IgD myeloma plasma cells clone from a subset of germinal center cells (particularly tonsillar), which are SigM−, IgD+, and CD38+, because these cells share many features, including increased incidence of λ chain expression, Cμ-Cδ isotype switches, and extensive (somatic) mutations in IgV genes.1 However, there is still a lack of agreement as to the precise cellular origin. Some researchers have suggested that the malignant clone is derived from a “pre-switched memory B-cell type,”7 whereas others have postulated that the clone is derived from an IgD-secreting plasma cell derived from germinal centers.1 Because of the rarity of the disease, possible mutations involved in this malignancy have not been fully defined, but studies reported to date indicate that these mutations may include changes in chromosome arm 1p and losses of the X chromosome, both of which are seen in other forms of multiple myeloma.8 There has been a case report of a patient with IgD myeloma hypodiploidy and a karyotype that includes loss of X and monosomy 13.8
For patients with IgD myeloma, prognosis can be predicted based on clinical features. Although it is not possible to use the standard myeloma staging systems, such as Durie and Salmon or the British Medical Research Council, both light chain type and white blood cell count are known to be associated with differences in prognosis. In this scheme, λ chains and white blood cell concentrations greater than 7000/μL predict a poorer prognosis.4 The response rate to initial chemotherapy for IgD myeloma is 58%, which is similar to that of other myeloma types.5 Multi-agent chemotherapy regimens, such as the vincristine, doxorubicin, and dexamethasone regimen, have been associated with a longer survival time. Stem cell transplantation may also be used as a future treatment.3
References
Reprints not available from the author.
Corresponding author: Kenneth W. Ryder, MD, PhD, Department of Pathology and Laboratory Medicine, Indiana University Hospital, UH 4550, 550 N University Blvd, Indianapolis, IN 46202 ([email protected]).