IgD Myeloma Report of a Case with Unusual Clinical and Immunologic Features RAFAEL VALENZUELA, M.D., SUGANTHA GOVINDARAJAN, M.D., RAYMOND TUBBS, D.O., SHARAD DEODHAR, M.D., PH.D., AND RONALD BUKOWSKI, M.D.
I G D MYELOMA is rare; the overall incidence of monoclonal IgD in a worldwide series is only 1.2%. Approximately 135 cases have been reported since its original description by Rowe and Fahey 5 ' 6 in 1963. In contrast to other myelomas, lambda-type light chains are found in 90% of these myelomas. 4 Among the light chains of M components, the kappa/lambda ratio is 2:1 in IgG, IgA, and IgM, whereas it is 1:9 in IgD. Bence Jones proteinemia is frequent, and Bence Jones proteinuria appears in almost all cases (92%). This report describes the clinical, cytologic and immunologic findings in a case of IgD kappa myeloma which presented diagnostic problems because of its unusual clinical and immunochemical features. Immunoelectrophoresis of IgD, purified by gel chromatography, was helpful in establishing the diagnosis. For comparison, we also present data from two other cases of IgD myelomas with lambda light chains found in our laboratory. Received May 9, 1977; received revised manuscript and accepted for publication September 1, 1978. Address reprint requests to Dr. Valenzuela: Department of Immunopathology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44106.
Department of Immunopathology, Cleveland Clinic Foundation, Cleveland, Ohio
Report of a Case A 48-year-old man sought treatment for low-back pain and weight loss of recent onset. Physical examination disclosed no abnormality. Roentgenograms of the skull and chest were noncontributory, a bone scan revealed increased uptake at L5-S1, and roentgenograms of the thoracic and lumbar spine revealed osteoporosis and compression fractures of T9 and T10. The erythrocyte count in peripheral blood was 5,300,000/mm3, leukocyte count, 10,900/mm3, with 72% neutrophils, 15% lymphocytes, and 13% monocytes. Hematocrit was 44% and hemoglobin, 14.42 g/dl. Serum calcium was 12.7 mg/dl; serum creatinine 1.7 mg/dl; blood urea nitrogen (BUN), 30 mg/100 ml. Serum electrophoresis repeatedly showed a slightly increased level of beta globulin but no monoclonal spike (Fig. 2). Urinalysis was negative for Bence Jones protein by immunoelectrophoresis. Examination of bone-marrow aspirates from the iliac crest showed plasmablasts, 2%; immature plasma cells, 2%; mature plasma cells, 10%; lymphocytes, 45% (Fig. 1). Quantitation of immunoglobulins by radial immunodiffusion showed the level of IgD to be 750 mg/dl; IgG, 570 mg/dl; IgA, 98 mg/dl; IgM, 37 mg/dl. Immunochemical studies are described below. Treatment with radiation therapy to the thoracic and lumbar spine was given, with subsequent relief of back pain. Intermittent courses of melphalan (6 mg/m2) and prednisone (100 mg) for four days, at four-week intervals, were also given. After two courses ofchemotherapy, serum immunoglobulin quantitation revealed IgD 58 mg/dl and slight increase in IgG (790 mg/dl) and IgM (47 mg/dl). Seven months later, the IgD level had returned to normal (4 mg/dl). Relapse, with increasing osseous lesions and an increase in IgD (22 mg/dl), occurred after 18 months, and was resistant to other therapy. At that time, bone marrow aspiration showed plasmablasts, 2%; immature plasma cells, 2%; lymphocytes, 25%.
Methods Immunoelectrophoresis Wells and troughs were cut in glass slides coated with ion agar. Samples of whole serum or concentrated urine (25x) were placed in the wells, and electrophoresis was carried out in a Laurell electrophoresis chamber at 6-10 volts/cm for one and a half hours. Specific antisera to IgG, IgA, IgM, and IgD (Hyland Laboratories, Costa Mesa, Calif.) and kappa and lambda (Dakopatts, Copenhagen, Denmark) were placed in troughs and al-
0002-9173/79/0800/0246 $00.75 © American Society of Clinical Pathologists
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Valenzuela, Rafael, Govindarajan, Sugantha, Tubbs, Raymond, Deodhar, Sharad, and Bukowski, Ronald: IgD myeloma. Report of a case with unusual clinical and immunologic features. Am J Clin Pathol 72: 246-250, 1979. A case of IgD myeloma in a 48-year-old Caucasian man is reported. The unusual features of this case included the absence of osteolytic lesions by x-ray, absence of anemia, absence of monoclonal spike on serum electrophoresis, association of kappa light chains, absence of Bence Jones proteinemia and Bence Jones proteinuria, and a remarkable, temporary clinical response to therapy. Immunoelectrophoresis of whole serum yielded a pattern consistent with IgD kappa monoclonal gammopathy. Immunoelectrophoresis of a pure serum IgD preparation, previously separated by gel chromatography (Sephadex G-200), revealed definitive information about an IgD kappa monoclonal gammopathy. Immunomicroscopic examination of bonemarrow smears showed the presence of delta and kappa chains only in the cytoplasm of plasma cells. (Key words: Multiple myeloma; Monoclonal gammopathy; Plasma cell dycrasia; Immunoelecrophoresis; Immunomicroscopy; Chromatography.)
Vol. 72 • No. 2
247
CASE REPORTS
\
l
^j/\j/4/>\jj 0 FIG. I. Bone-marrow smear, showing plasma cell infiltration (arrow). Wright's stain, x 1,000.
a, ALBUMIN
FIG. 2. Serum electrophoresis with no monoclonal spike.
were rehydrated in phosphate-buffered saline solution (PBS) (0.02 M, pH 7.5) and Tris buffer, pH 9.4 (Tris base, 5.47 g; NaCl, 6 g; Tris HCl, 0.76 g, in 1,000 ml distilled water), and then incubated with the antisera
Chromatography Gel filtration on Sephadex G-200® was performed by use of a 4 x 100-cm column, equilibrated in 0.2 MNaCl and 0.2 M Tris HCl (pH, 8.0). One milliliter of the whole serum was applied to the column and the proteins were eluted with the same buffer and collected in 6-ml fractions. Proteins in this eluate were identified by measuring the optical density at 280 nm, by use of a Beckman® ultraviolet spectrophotometer. Optical density was traced in relation to the fraction numbers and peaks of protein concentrations were identified. By use of Ouchterlony plates, it was found that Peak I contained IgD and Peak II contained IgG (Fig. 4). Quantitation of Immunoglobulins This was done by the radial immunodiffusion method using plates from Hyland Laboratories (Costa Mesa, Calif.). Immunomicroscopy Immunomicroscopy was performed utilizing the direct immunoperoxidase technic and monospecific antibodies conjugated with horseradish peroxidase (Bioware Co., Wichita, Kans.). The specimens studied included a Zenker-fixed bone-marrow biopsy and airdried bone-marrow aspirates. Five-micrometer sections from the biopsy specimen were placed on glass slides and deparaffinized in acetone. All specimens
FIG. 3. Immunoelectrophoretic pattern of whole serum, showing a slightly distorted K precipitation arc. The area of distortion lines up with the IgD precipitation arc. No K distortion or D precipitation arc is observed in the control serum. C = control normal human serum (2/il in each well); P = patient's serum (2 /i,l in each well); 1 = human gamma globulin antiserum; G = y antiserum; A = a antiserum; K = K antiserum; L = X antiserum (50 ^.1 in each trough). + represents the anode.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
lowed to diffuse and react in a moist chamber for 48 hours. The slides showing precipitation arcs were then stained with Ponceau red S for 20 min. This procedure was repeated with pure IgD-containing samples, separated as described below.
az
i
M
VALENZUELA ET AL.
248
A.J.C.P. • August 1979
.260 I.G
ALBUM*
.220
Pi
.180-
.140-
Pi K
3 -100
Pi
.060
D .020 29 35 45 55 FRACTIONS OF ELUATE IN ML.
65
FIG. 4. Sephadex G-200gel chromatography. Notice the two distinct protein peaks for IgD and IgG.
(peroxidase antihuman G, A, M, D, E, kappa and lambda) for an hour. Next slides were rinsed in PBS and the antigen-antibody complexes fixed in denatured alcohol for 10 min. the specimens were then washed in PBS-Tween-80® (Sigma Chemical Co., St. Louis, Mo.: PBS, 150 ml with 0.05 ml Tween-80) for 10 min and overlayed with the substrate solution (90 mg of 3,3diaminobenzidine tetrachloride and 0.02 ml of 30% H 2 0 2 in 100 ml PBS). This was followed by washing in PBS, counterstaining with 1% methyl green, dehydrating in alcohol and Xylene®, and mounting with
J
0
#
*
FIG. 5. Positive, dark brown reaction in the cytoplasm of bonemarrow plasma cells (arrow) stained with peroxidase-IgD antiserum. Specimen counterstained with methyl green, x 1,000.
L Pi
V
Pi FIG. 6. Immunoelectrophoresis of the first peak obtained by gel chromatography, showing a conclusive IgD kappa monoclonal pattern. The first well contains control normal human serum (C). The remaining wells (PI) contain patients' IgD (Peak I). I, human immunoglobulin antiserum; G, y antiserum; K, « antiserum; L, X antiserum; A, a antiserum.
Permount® for light microscopic examination. All the antisera were found to be active and monospecific by Immunoelectrophoresis against normal human serum and IgD myeloma serum. IgD and kappa antisera did not stain the bone-marrow plasma cells of a patient who had immunochemically and immunohistologically proved IgG (lambda) myeloma. However, positive reactions were detected with IgG and lambda antisera. The unlabeled (PAP) immunoperoxidase procedure was also utilized in this study. The deparaffinized, rehydrated paraffin-embedded sections of formalin-fixed, aspirated bone marrow were overlayed with 20% normal goat serum in PBS for 20 min. Monospecific rabbit anti-IgG, IgA, IgM, IgD, kappa and lambda (Behring Diagnostics; Cappel Laboratories) were overlayed on the sections, and an overnight (18-hour) incubation with primary antibody done. The sections were gently washed with 5% normal goat serum in PBS and goat antirabbit IgG (Cappel), 1:50, overlayed on the sections. After a subsequent washing procedure, the
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
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CASE REPORTS
Vol. 72 • No. 2
rabbit peroxidase-antiperoxidase complex (Cappel), 1:50, was incubated with the sections for 10 min, and the slides washed in PBS for 10 min. The substrate chromogen solution consisted of 7 mg of 3,3-diaminobenzidine in 10 ml of PBS with .04 ml of 30% hydrogen peroxidase (H 2 0 2 ; Fisher Scientific). Sections were then counterstained with hematoxylin, dehydrated in graded alcohol, and mounted with Permount. Controls consisted of a substitution of normal goat serum for the primary antibody for negative controls, and a substitution of an absorbed antibody in the case of the anti-IgD and anti-kappa antisera. Results
Discussion Problems involved in the diagnosis of this case of IgD kappa myeloma deserve further discussion. Serum protein electrophoresis revealed no M spike; this was an unexpected finding, since the sensitivity of this technic for monoclonal protein is about 200 mg/dl, and the IgD level was 750 mg/dl. Similar observations have been reported in other cases of IgD (kappa) myeloma.4,9 Immunoelectrophoresis of the whole serum
Table I. Frequencies of IgD M Components (1966-1976) at Cleveland Clinic IgG
IgA
IgM
IgD
Total
Number of cases Percentage of cases
99 60.7
47 28.8
14 8.5
3 1.8
163 100
Light chains Kappa Lambda
57 42
21 26
12 2
1 2
91 72
was consistent with IgD kappa monoclonal gammopathy. More definitive information was obtained after separating the various immunoglobulins by use of Sephadex G-200 column chromatography and repeating the immunoelectrophoresis with the eluates. IgD, with the molecular weight of 190,000, appeared in the first peak before IgG, with a molecular weight of 160,000 (Fig. 4). It was clear that the heavy IgD chains were associated with monoclonal kappa light chains only (Fig. 6). The frequencies of various classes of immunoglobulins among M components correspond roughly to their physiologic concentrations. In our series of 163 cases of monoclonal gammopathies, IgD comprised 1.8% (three cases; Table 1). A remarkable preponderance of lambda-type light chains with IgD myeloma (90%) has been reported.4 Bence Jones proteinuria was found in 92% of IgD myelomas.4 Delta heavy chain disease has not been reported yet. The survival figures for IgD myelomas were much shorter when compared with other myelomas. Renal failure, associated with excessive Bence Jones proteinuria, is the major cause of poor survival in this group.4 Staging criteria for multiple myeloma exist for IgG, IgA, and Bence Jones variants; however, they have not been applied
Table 2. Clinical Manifestations of IgD Kappa Myelomas and IgD Lambda Myelomas in the Literature Response to Therapy
Age (Years), Sex
Myeloma Type
Bence Jones Proteinuria
Osteolytic Lesions
Anemia*
Renal Failuret
Present series Patient 1
48, M
DK
-
-
-
-
Good
Patient 2 Patient 3
63, F 55, M
DX D\
+ +
+ +
+ +
+ +
Poor Poor
2 years; still alive
I G D MYELOMA is rare; the overall incidence of monoclonal IgD in a worldwide series is only 1.2%. Approximately 135 cases have been reported since its original description by Rowe and Fahey 5 ' 6 in 1963. In contrast to other myelomas, lambda-type light chains are found in 90% of these myelomas. 4 Among the light chains of M components, the kappa/lambda ratio is 2:1 in IgG, IgA, and IgM, whereas it is 1:9 in IgD. Bence Jones proteinemia is frequent, and Bence Jones proteinuria appears in almost all cases (92%). This report describes the clinical, cytologic and immunologic findings in a case of IgD kappa myeloma which presented diagnostic problems because of its unusual clinical and immunochemical features. Immunoelectrophoresis of IgD, purified by gel chromatography, was helpful in establishing the diagnosis. For comparison, we also present data from two other cases of IgD myelomas with lambda light chains found in our laboratory. Received May 9, 1977; received revised manuscript and accepted for publication September 1, 1978. Address reprint requests to Dr. Valenzuela: Department of Immunopathology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44106.
Department of Immunopathology, Cleveland Clinic Foundation, Cleveland, Ohio
Report of a Case A 48-year-old man sought treatment for low-back pain and weight loss of recent onset. Physical examination disclosed no abnormality. Roentgenograms of the skull and chest were noncontributory, a bone scan revealed increased uptake at L5-S1, and roentgenograms of the thoracic and lumbar spine revealed osteoporosis and compression fractures of T9 and T10. The erythrocyte count in peripheral blood was 5,300,000/mm3, leukocyte count, 10,900/mm3, with 72% neutrophils, 15% lymphocytes, and 13% monocytes. Hematocrit was 44% and hemoglobin, 14.42 g/dl. Serum calcium was 12.7 mg/dl; serum creatinine 1.7 mg/dl; blood urea nitrogen (BUN), 30 mg/100 ml. Serum electrophoresis repeatedly showed a slightly increased level of beta globulin but no monoclonal spike (Fig. 2). Urinalysis was negative for Bence Jones protein by immunoelectrophoresis. Examination of bone-marrow aspirates from the iliac crest showed plasmablasts, 2%; immature plasma cells, 2%; mature plasma cells, 10%; lymphocytes, 45% (Fig. 1). Quantitation of immunoglobulins by radial immunodiffusion showed the level of IgD to be 750 mg/dl; IgG, 570 mg/dl; IgA, 98 mg/dl; IgM, 37 mg/dl. Immunochemical studies are described below. Treatment with radiation therapy to the thoracic and lumbar spine was given, with subsequent relief of back pain. Intermittent courses of melphalan (6 mg/m2) and prednisone (100 mg) for four days, at four-week intervals, were also given. After two courses ofchemotherapy, serum immunoglobulin quantitation revealed IgD 58 mg/dl and slight increase in IgG (790 mg/dl) and IgM (47 mg/dl). Seven months later, the IgD level had returned to normal (4 mg/dl). Relapse, with increasing osseous lesions and an increase in IgD (22 mg/dl), occurred after 18 months, and was resistant to other therapy. At that time, bone marrow aspiration showed plasmablasts, 2%; immature plasma cells, 2%; lymphocytes, 25%.
Methods Immunoelectrophoresis Wells and troughs were cut in glass slides coated with ion agar. Samples of whole serum or concentrated urine (25x) were placed in the wells, and electrophoresis was carried out in a Laurell electrophoresis chamber at 6-10 volts/cm for one and a half hours. Specific antisera to IgG, IgA, IgM, and IgD (Hyland Laboratories, Costa Mesa, Calif.) and kappa and lambda (Dakopatts, Copenhagen, Denmark) were placed in troughs and al-
0002-9173/79/0800/0246 $00.75 © American Society of Clinical Pathologists
246
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
Valenzuela, Rafael, Govindarajan, Sugantha, Tubbs, Raymond, Deodhar, Sharad, and Bukowski, Ronald: IgD myeloma. Report of a case with unusual clinical and immunologic features. Am J Clin Pathol 72: 246-250, 1979. A case of IgD myeloma in a 48-year-old Caucasian man is reported. The unusual features of this case included the absence of osteolytic lesions by x-ray, absence of anemia, absence of monoclonal spike on serum electrophoresis, association of kappa light chains, absence of Bence Jones proteinemia and Bence Jones proteinuria, and a remarkable, temporary clinical response to therapy. Immunoelectrophoresis of whole serum yielded a pattern consistent with IgD kappa monoclonal gammopathy. Immunoelectrophoresis of a pure serum IgD preparation, previously separated by gel chromatography (Sephadex G-200), revealed definitive information about an IgD kappa monoclonal gammopathy. Immunomicroscopic examination of bonemarrow smears showed the presence of delta and kappa chains only in the cytoplasm of plasma cells. (Key words: Multiple myeloma; Monoclonal gammopathy; Plasma cell dycrasia; Immunoelecrophoresis; Immunomicroscopy; Chromatography.)
Vol. 72 • No. 2
247
CASE REPORTS
\
l
^j/\j/4/>\jj 0 FIG. I. Bone-marrow smear, showing plasma cell infiltration (arrow). Wright's stain, x 1,000.
a, ALBUMIN
FIG. 2. Serum electrophoresis with no monoclonal spike.
were rehydrated in phosphate-buffered saline solution (PBS) (0.02 M, pH 7.5) and Tris buffer, pH 9.4 (Tris base, 5.47 g; NaCl, 6 g; Tris HCl, 0.76 g, in 1,000 ml distilled water), and then incubated with the antisera
Chromatography Gel filtration on Sephadex G-200® was performed by use of a 4 x 100-cm column, equilibrated in 0.2 MNaCl and 0.2 M Tris HCl (pH, 8.0). One milliliter of the whole serum was applied to the column and the proteins were eluted with the same buffer and collected in 6-ml fractions. Proteins in this eluate were identified by measuring the optical density at 280 nm, by use of a Beckman® ultraviolet spectrophotometer. Optical density was traced in relation to the fraction numbers and peaks of protein concentrations were identified. By use of Ouchterlony plates, it was found that Peak I contained IgD and Peak II contained IgG (Fig. 4). Quantitation of Immunoglobulins This was done by the radial immunodiffusion method using plates from Hyland Laboratories (Costa Mesa, Calif.). Immunomicroscopy Immunomicroscopy was performed utilizing the direct immunoperoxidase technic and monospecific antibodies conjugated with horseradish peroxidase (Bioware Co., Wichita, Kans.). The specimens studied included a Zenker-fixed bone-marrow biopsy and airdried bone-marrow aspirates. Five-micrometer sections from the biopsy specimen were placed on glass slides and deparaffinized in acetone. All specimens
FIG. 3. Immunoelectrophoretic pattern of whole serum, showing a slightly distorted K precipitation arc. The area of distortion lines up with the IgD precipitation arc. No K distortion or D precipitation arc is observed in the control serum. C = control normal human serum (2/il in each well); P = patient's serum (2 /i,l in each well); 1 = human gamma globulin antiserum; G = y antiserum; A = a antiserum; K = K antiserum; L = X antiserum (50 ^.1 in each trough). + represents the anode.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
lowed to diffuse and react in a moist chamber for 48 hours. The slides showing precipitation arcs were then stained with Ponceau red S for 20 min. This procedure was repeated with pure IgD-containing samples, separated as described below.
az
i
M
VALENZUELA ET AL.
248
A.J.C.P. • August 1979
.260 I.G
ALBUM*
.220
Pi
.180-
.140-
Pi K
3 -100
Pi
.060
D .020 29 35 45 55 FRACTIONS OF ELUATE IN ML.
65
FIG. 4. Sephadex G-200gel chromatography. Notice the two distinct protein peaks for IgD and IgG.
(peroxidase antihuman G, A, M, D, E, kappa and lambda) for an hour. Next slides were rinsed in PBS and the antigen-antibody complexes fixed in denatured alcohol for 10 min. the specimens were then washed in PBS-Tween-80® (Sigma Chemical Co., St. Louis, Mo.: PBS, 150 ml with 0.05 ml Tween-80) for 10 min and overlayed with the substrate solution (90 mg of 3,3diaminobenzidine tetrachloride and 0.02 ml of 30% H 2 0 2 in 100 ml PBS). This was followed by washing in PBS, counterstaining with 1% methyl green, dehydrating in alcohol and Xylene®, and mounting with
J
0
#
*
FIG. 5. Positive, dark brown reaction in the cytoplasm of bonemarrow plasma cells (arrow) stained with peroxidase-IgD antiserum. Specimen counterstained with methyl green, x 1,000.
L Pi
V
Pi FIG. 6. Immunoelectrophoresis of the first peak obtained by gel chromatography, showing a conclusive IgD kappa monoclonal pattern. The first well contains control normal human serum (C). The remaining wells (PI) contain patients' IgD (Peak I). I, human immunoglobulin antiserum; G, y antiserum; K, « antiserum; L, X antiserum; A, a antiserum.
Permount® for light microscopic examination. All the antisera were found to be active and monospecific by Immunoelectrophoresis against normal human serum and IgD myeloma serum. IgD and kappa antisera did not stain the bone-marrow plasma cells of a patient who had immunochemically and immunohistologically proved IgG (lambda) myeloma. However, positive reactions were detected with IgG and lambda antisera. The unlabeled (PAP) immunoperoxidase procedure was also utilized in this study. The deparaffinized, rehydrated paraffin-embedded sections of formalin-fixed, aspirated bone marrow were overlayed with 20% normal goat serum in PBS for 20 min. Monospecific rabbit anti-IgG, IgA, IgM, IgD, kappa and lambda (Behring Diagnostics; Cappel Laboratories) were overlayed on the sections, and an overnight (18-hour) incubation with primary antibody done. The sections were gently washed with 5% normal goat serum in PBS and goat antirabbit IgG (Cappel), 1:50, overlayed on the sections. After a subsequent washing procedure, the
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
Pi IS
CASE REPORTS
Vol. 72 • No. 2
rabbit peroxidase-antiperoxidase complex (Cappel), 1:50, was incubated with the sections for 10 min, and the slides washed in PBS for 10 min. The substrate chromogen solution consisted of 7 mg of 3,3-diaminobenzidine in 10 ml of PBS with .04 ml of 30% hydrogen peroxidase (H 2 0 2 ; Fisher Scientific). Sections were then counterstained with hematoxylin, dehydrated in graded alcohol, and mounted with Permount. Controls consisted of a substitution of normal goat serum for the primary antibody for negative controls, and a substitution of an absorbed antibody in the case of the anti-IgD and anti-kappa antisera. Results
Discussion Problems involved in the diagnosis of this case of IgD kappa myeloma deserve further discussion. Serum protein electrophoresis revealed no M spike; this was an unexpected finding, since the sensitivity of this technic for monoclonal protein is about 200 mg/dl, and the IgD level was 750 mg/dl. Similar observations have been reported in other cases of IgD (kappa) myeloma.4,9 Immunoelectrophoresis of the whole serum
Table I. Frequencies of IgD M Components (1966-1976) at Cleveland Clinic IgG
IgA
IgM
IgD
Total
Number of cases Percentage of cases
99 60.7
47 28.8
14 8.5
3 1.8
163 100
Light chains Kappa Lambda
57 42
21 26
12 2
1 2
91 72
was consistent with IgD kappa monoclonal gammopathy. More definitive information was obtained after separating the various immunoglobulins by use of Sephadex G-200 column chromatography and repeating the immunoelectrophoresis with the eluates. IgD, with the molecular weight of 190,000, appeared in the first peak before IgG, with a molecular weight of 160,000 (Fig. 4). It was clear that the heavy IgD chains were associated with monoclonal kappa light chains only (Fig. 6). The frequencies of various classes of immunoglobulins among M components correspond roughly to their physiologic concentrations. In our series of 163 cases of monoclonal gammopathies, IgD comprised 1.8% (three cases; Table 1). A remarkable preponderance of lambda-type light chains with IgD myeloma (90%) has been reported.4 Bence Jones proteinuria was found in 92% of IgD myelomas.4 Delta heavy chain disease has not been reported yet. The survival figures for IgD myelomas were much shorter when compared with other myelomas. Renal failure, associated with excessive Bence Jones proteinuria, is the major cause of poor survival in this group.4 Staging criteria for multiple myeloma exist for IgG, IgA, and Bence Jones variants; however, they have not been applied
Table 2. Clinical Manifestations of IgD Kappa Myelomas and IgD Lambda Myelomas in the Literature Response to Therapy
Age (Years), Sex
Myeloma Type
Bence Jones Proteinuria
Osteolytic Lesions
Anemia*
Renal Failuret
Present series Patient 1
48, M
DK
-
-
-
-
Good
Patient 2 Patient 3
63, F 55, M
DX D\
+ +
+ +
+ +
+ +
Poor Poor
2 years; still alive
