0. Fig. 2(5) Eosinophilic IgD crystals in tubules
Immunoglobulin D (IgD) Multiple Myeloma with Rapidly Progressing Renal Failure
Dr. Modi. J, Dr. Eter. A, Dr. El-Sayegh S, Dr. El-Charabaty. E
Nephrology Division, Department of Internal Medicine, Staten Island University Hospital, Staten Island (SIUH), NY
Contact
ratio is a characteristic feature of IgD MM, Shimamoto et al reported it in 82%.(4) The combination of increased creatinine levels, hypercalcemia, hyperuricemia, and light chain excretion is often associated with renal insufficiency in IgD MM.(5) Over last decade, multiple randomized trials have shown the superiority of high-doses of chemotherapy (Thalidomide/Bortezomib, Dexamethasone) with autologous stem cell transplantation (HDT/ASCT) over standard therapy (Melphalan, Vincristine, Adriamycin, Dexamethasone). New immunomodulatory agents and proteasome inhibitors in HDT/ASCT program is likely to improve the outcome of IgD MM.
Discussion
Introduction
Hospital Course
In multiple myeloma, IgG, IgA, and light chains predominate, with a prevalence of 52%, 21%, and 16%, respectively, comprising almost 90% of all myeloma types. The remainder consists of IgD, IgE, IgM, and nonsecretory types.(2)
His S. Cr deteriorated next day to 8.5 mg/dL and became anuric, requiring hemodialysis.
Serology was positive for Serum free λ chain level of 8947 mg/L as well with free κ/λ <0.01. Serum IgD level was remarkably elevated (27300 mg/L).
The results of SPEP, UPEP and Immunofixation were also supportive of diagnosis of IgD MM.
Skeletal survey: 1 cm lytic lesion in the iliac crest.
The bone marrow biopsy was positive for plasma cell hypercellularity (70-80%) and flow cytometry showed 8% monoclonal IgD λ plasma cells.
Kidney biopsy was not performed in light of confirmed diagnosis with bone marrow biopsy.
Fluorescence in-situ Hybridization (FISH) showed positive 1q21 copies in 7.5% cells consistent with plasma cell myeloma with adverse prognosis for event free and overall survival
The patient’s symptoms had improved with RRT and he was discharged home on chemotherapy (Bortezomib and Dexamethasone) and hemodialysis. Six months later, patient received bone marrow transplant achieving hematological remission of his myeloma. However, he still remains hemodialysis dependent.
Immunoglobulin (Ig) D multiple myeloma (IgD MM) is a rare subtype of myeloma, with incidence of less than 2% of all myelomas (1) and associated with poorer prognosis than other types of myeloma subtypes.
IgD secreting plasma cells originate from germinal center B cells due to somatic hypermutation of IgV regions. Compared to IgG and IgA, serum concentration of IgD is much lower. Thus, it may only show a small or absent M-spike on SPEP posing a diagnostic challenge. IgD MM has been reported to have a more aggressive course and a poor prognosis, with
Light Chain Cast Nephropathy (LCCN): The filtered monoclonal light chains form intratubular casts and obstruct the tubular flow, incite foreign
body reaction and cause tubular fibrosis. In addition, light chains can also cause direct toxicity to proximal tubular cells and intracellular crystal formation.
Summary
Case Presentation
IgD MM is rare (1.5-2%), has onset at a younger age with advanced disease at time of diagnosis and poor prognosis compared with other types of MM. All MM patients with light chain proteinuria and small or absent M-spike should be evaluated for IgD MM. More trials with HDT/ASCT are needed to formulate therapeutic guideline for better outcome.
62 year old Caucasian male, smoker with past medical history of hypertension, presented to ED with complaints of lower abdominal pain, constipation, decreased urination and weakness progressively over two weeks.
Physical exam was unremarkable except mildly elevated BP (155/78 mmhg). Insertion of Foley catheter yielded approx. 300 ml of urine and stool guaiac was negative.
Laboratory studies showed BUN 35 mg/dL, S. Cr 5.99 mg/dL, hgb 8.7 g/dL, A/G ratio 0.84 and corrected S.Ca 10.6 mg/dL. Urine dipstick showed 100 protein, + blood and TP/Cr ratio was 23.
He was admitted for further work up of rapidly progressing renal failure.
patients having a median survival of less than 2 years prior to the availability of novel agents and use of autologous transplantation.(3) The bias for λ light chain expression with a reversed light chain
References
Bladé J, Kyle RA: Nonsecretory myeloma, immunoglobulin D myeloma, and plasma cell leukemia. ematol Oncol Clin North Am 1999, 13:
Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clinic Proc. 2003;78:21-33.
Bladé J, Lust JA, Kyle RA. Immunoglobulin D multiple myeloma: presenting features, response to therapy, and survival in a series of 53 cases. J Clin Oncol. 1994;12:
Shimamoto Y, Anami Y, Yamaguchi M. A new risk grouping for IgD myeloma based on analysis of 165 Japanese patients. Eur J Haematol.1991;47:262-7.
Kyle RA. Multiple myeloma: review of 869 cases. Mayo Clinic proceedings. Mayo Clinic. 1975;50:29-40
Ce´cile Toly-Ndour et al. Acute renal failure with lambda light chain derived crystals in a patient with IgD myeloma. Nephrol Dial Transplant (2011) 26: 3057–3059
Fig.1*(a) Bone marrow biopsy (b)IgD M-spike
Fig. 2(5) Eosinophilic IgD crystals in tubules
* Courtesy Dr. Ebaee. A, Dept of Pathology, SIUH