Beyond Monoclonal Gammopathy of Undetermined Significance, Clinical Spectrum of Immunoglobulin M Gammopathy: A Case Series with Focus on the Diagnostic and Management Challenges

Figures & data

Table 1. A summary of laboratory results of the three cases: type I cryoglobulinemia, type II cryoglobulinemia, and Bing–Neel syndrome.

Test	Case 1	Case 2	Case 3	Reference
Hemoglobin	9.9	8.1	13.7	11.5–15.5 g/dl
White blood cells	3.17	6.63	7.07	3.70–11.00 k/ul
Neutrophils	51.1	75.0	58.8
Lymphocytes	32.5	16.4	31.2
Platelets	229	201	261	150–400 k/ul
Creatinine	1.36	1.73	0.73	0.58–0.96 mg/dl
Blood urea nitrogen	24	41	12	7–21 mg/dl
Sodium	139	135	126	136–144 mmol/l
Total bilirubin	0.7	0.2	0.7	0.2–1.3 mg/dl
Alkaline phosphatase	52	128	79	34–123 U/l
Alanine amino transferase	11	8	37	7–38 U/l
Calcium	10.4	8.0	9.0	8.5–10.2 mg/dl
Phosphorus	4.4	2.8	3.8	2.7–4.8 mg/dl
Albumin	4.2	2.8	3.7	3.9–4.9 g/dl
Lactate dehydrogenase	201	159	229	135–214 U/l
Urine microscopy	Few granular casts, 10–20 normomorphic RBCs, 5–10 WBCs	Few granular casts, 3–5 normomorphic red blood cells, 3–5 white blood cells		Casts are per low-power field, cells are per high-power field
Urine protein-to-creatinine ratio	1.5	5.5		<0.2
Serum protein electrophoresis interpretation	M protein identified	M protein identified	M protein identified
M protein location	Gamma fraction	Gamma fraction	Gamma fraction
M protein concentration	0.93	0.09 and 0.21	0.18	0.00 gm/dl
Serum kappa to lambda ratio	5.91	3.10	0.93	0.26–1.65
Complement 3	53	54		86–166 mg/dl
Complement 4	<2	<2		13–46 mg/dl
Anti-nuclear antibodies	1:640	>1:1,280		Negative
Anti-nuclear antibody pattern	Speckled	Centromere
SSA antibody	Positive	Positive		Negative
SSB antibody	Positive	Positive		Negative
Rheumatoid factor	56			<16 IU/ml
Cryoglobulin, qualitative	Negative	Positive	Negative	Negative
IgA cryoprecipitate		3		0 mg/dl
IgG cryoprecipitate		17		0 mg/dl
IgM cryoprecipitate		26		0 mg/dl
Human immunodeficiency virus 1/2	Negative	Negative	Negative	Negative
Hepatitis B surface antigen	Negative	Negative		Negative
Hepatitis B surface antibody	Negative	Negative		Negative
Hepatitis B core antibody	Negative	Negative		Negative
Hepatitis C antibody	Negative	Negative		Negative

Table 2. Formal diagnostic criteria of type I cryoglobulinemia, type II cryoglobulinemia, and Bing–Neel syndrome.

	Case 1: type I cryoglobulinemia	Case 2: type II cryoglobulinemia	Case 3: Bing–Neel syndrome
Diagnostic Criteria	○ Cryocrit level (>10%) ○ Immunochemical analysis/immunofixation (IgM heavy chains) ○ Biopsy (immune complex vasculitis)	○ Immunochemical analysis/immunofixation (polyclonal IgG chains) ○ Cryocrit level (2–7%) ○ Biopsy (immune complex vasculitis)	○ Cerebral spinal fluid analysis (clonal B cells) ○ MRI of CNS (leptomeningeal or parenchymal involvement)