Diagnosis for Chinese patients with light chain amyloidosis: a scoping review

Figures & data

Figure 1. PRISMA flow diagram for article selection for analysis.

Table 1. Summary of patients’ characteristics based on 43 included studies.

Characteristics	No. of reported patients (Percentage)	No. of studies
Age	1904	27
Reported mean of the age 49 to 61 years	1494 (78.5%)	22
Reported median of age 43 to 63 years	545 (28.6%)	8
Gender	2060	31
Female	761 (36.9%)	32
Male	1299 (63.1%)	30
Primary or secondary	686	13
Primary	656 (95.6%)	13
Secondary	30 (4.4%)	3
Type of light chains	1366	25
Lambda	1106 (81.0%)	25
Kappa	260 (19.0%)	24
Mayo 2004 cardiac staging system	170	2
I	35 (20.6%)	2
II	57 (33.5%)	2
III	62 (36.5%)	2
Mayo 2012 cardiac staging system	537	5
I	171 (31.8%)	5
II	135 (25.1%)	5
III	121 (22.5%)	5
IV	61 (11.4%)	5
Clonal plasma cell in bone marrow	695	10
≥10%	32 (5.0%)	2

Table 2. Summary of biopsy sites and related sample size of the patients based on 40 included studies (n = 2101).

Biopsy sites	Study		Sample size
	Number	Proportion	Number	Proportion
Renal	27	67.5%	1367	65.1%
Bone marrow	16	40.0%	656	31.2%
Tongue	7	17.5%	78	3.7%
Cardiac	6	15.0%	63	3.0%
Liver	6	15.0%	67	3.2%
Abdominal wall fat	5	12.5%	136	6.5%
Rectal mucosa	5	12.5%	334	15.9%
Fat	4	10.0%	76	3.6%
Skin and fat	3	7.5%	262	12.5%
Skin	2	5.0%	17	0.8%
Labial gland	2	5.0%	64	3.0%
Lung	1	2.5%	1	0.0%
Skin or fat	1	2.5%	15	0.7%

Spleen, gingiva, gastrointestinal tract, rectum, sural nerve, buccal mucosa, lymph gland and muscle were also reported in a small number of the literatures.

Table 3. Summary of diagnostic methods for light chains classification and different M protein identification in 43 included studies.

Measurement	Study		Sample size
	Number	Proportion	Number	Proportion
Types of light chains classification method	39		2450
Immunohistochemistry	15	34.9%	593	24.2%
Immunofluorescence	12	27.9%	897	36.7%
Electron microscopy	10	23.3%	836	34.2%
Immunoelectron microscopy (SEM)	2	4.7%	282	11.5%
Mass Spectrometry	0	0.0%	0	0.0%
M protein identification	51		2447
Serum free light chain	19	44.2%	1402	57.3%
Blood immunofixation electrophoresis	8	18.6%	723	29.5%
Urine free light chain	7	16.27%	265	10.8%
Blood and urine immunofixation electrophoresis	6	14.0%	167	6.8%
Blood or urine immunofixation electrophoresis	3	7.0%	100	4.1%
Serum or urine free light chain	2	4.7%	60	2.5%
Blood serum protein electrophoresis	1	2.3%	59	2.4%
Urine serum protein electrophoresis	1	2.3%	7	0.3%
Urine immunofixation electrophoresis	1	2.3%	87	3.6%
Blood/urine SPE	0	0.0%	0	0.0%
Urine Bence-Jone protein (urine)	3	7.0%	152	6.2%

SEM: the scanning electron microscopy; SPE: serum protein electrophoresis.

Table 4. The performance of diagnostic methods for detecting amyloidosis in China.

Measurement	Study ID	Positive events	Sample size	Sensitivity (%, 95% CI)	Specificity (%)	AUC (95% CI)
Biopsy
Congo red
Abdominal wall fat	Xu et al. [67]	37	54	68.5
	Xu et al. [31]	16	21	76.2
Abdominal wall fat and labial gland	Xu et al. [67]	35	41	85.4
Bone marrow	Xu et al. [67]	19	57	33.3
	Xu et al. [31]	10	21	47.6
	Wang et al. [64]	3	20	15
Labial gland	Xu et al. [67]	27	43	62.8
	Xu et al. [31]	13	21	61.9
Liver	Xu et al. [67]	1		50
Lung	Xu et al. [67]	1	1	100
Rectal mucosal	Li et al. [41]	167	176	94.9 (92–98)
	Li et al. [61] (Test Cohort)	127	134	94.8 (91.0–98.5)
	Li et al. [61] (Validation Cohort)	51	54	94.4 (87–100.0)
Renal	Zhang et al. [42]	14	14	100
	Xu et al. [67]	9	12	75
	Wang et al.2020b	5	6	83.3
	Xu et al. [31]	2	2	100
Skin	Wang et al. [64]	6	11	54.5
Skin and fat	Li et al. [41]	124	134	92.5 (88–97)
	Li et al. [61] (Test Cohort)	108	121	89.3 (83.5–94.2)
	Li et al. [61] (Validation Cohort)	47	51	92.2 (84.3–98.0)
Skin and fat and rectal mucosal	Li et al. [41]	105	124	84.7
Skin and fat or rectal mucosal	Li et al. [61] (Test Cohort)	89	90	98.9 (96.7–100.0)
	Li et al. [61] (Validation Cohort)	46	46	100
Spleen	Xu et al. [67]	1	1	100
Tongue	Wang et al. [64]	1	3	33.3
Deposit sites of amyloid
Skin and fat − Dermis	Li et al. [61]	−	155	45.8 (38.1–53.5)
Skin/fat − Subcutaneous tissue	Li et al. [61]	−	155	58.7 (50.3–66.5)
Skin and fat − Blood vessel	Li et al. [61]	−	155	36.1 (28.4–43.2)
Rectal mucosa − Mucosal layer	Li et al. [61]	−	178	42.7 (34.8–50.0)
Rectal mucosa − Submucosa layer	Li et al. [61]	−	178	40.5 (33.7–47.8)
Rectal mucosa − Blood vessel	Li et al. [61]	−	178	62.9 (55.1–70.2)
Immunofluorescence
Skin and fat	Li et al. [61] (Test Cohort)	30	37	81.1 (67.6–91.9)
	Li et al. [61] (Validation Cohort)	8	10	80
Rectal mucosal	Li et al. [61] (Test Cohort)	50	59	84.7 (74.6–93.2)
	Li et al. [61] (Validation Cohort)	34	37	91.9 (83.8–100)
Skin and fat or Rectal mucosal	Li et al. [61] (Test Cohort)	13	15	86.7
	Li et al. [61] (Validation Cohort)	7	7	100
Classification and identification methods
Types of light chains classification method
Immunohistochemistry	Zhai et al. [68]	21	25	84	−	−
Immunohistochemistry and serum free light chain or immunofixation electrophoresis	Zhai et al. [68]	24	25	96	−	−
Serum free light chain	Li et al. [41]	98	186	52.7	−	−
	Zhai et al. [68]	19	25	76	−	−
Serum free light chain and immunofixation electrophoresis	Zhai et al. [68]	22	25	88	−	−
	Zhou et al. [44]	−	625	65.6	98	0.659
	Yao et al. [45]	63	87	72.4	−	−
	Zhou et al. [44] (40–60 yr)	−	402	50	98	0.689
	Zhou et al. [44] (older than 60 yr)	−	223	81.3	98	0.585
M protein identification
Blood and urine immunofixation electrophoresis	Zhou et al. [44]	−	625	75	97.6	0.863 (0.832–0.894)
	Yao et al. [45]	105	157	66.9	−	−
	Zhou et al. [44] (40–60 yr)	−	402	68.8	97.7	0.832
	Zhou et al. [44] (older than 60 yr)	−	223	81.3	97.6	0.894
Blood immunofixation electrophoresis	Fan et al. [40]	66	112	58.9	−	−
	Li et al. [41]	83	161	51.6	−	−
	Zhou et al. [44]	−	625	56.3	98.6	0.653
	Yao et al. [45]	89	156	57.1	−	−
	Sa et al. [59]	71	119	59.7	−	−
	Zhou et al. [44] (40–60 yr)	−	402	43.8	98.6	0.684
	Zhou et al. [44] (older than 60 yr)	−	223	68.6	98.5	0.578
Immunofixation electrophoresis	Xu et al. [31]	18	21	85.7	−	−
	Zhai et al. [68]	17	25	68	−	−
Serum free light chain	Li et al. [41]	98	186	52.7	−	−
	Zhai et al. [68]	19	25	76	−	−
Serum free light chain and immunofixation electrophoresis	Zhai et al. [68]	22	25	88	−	−
	Zhou et al. [44]	−	625	65.6	98	0.659
	Yao et al. [45]	63	87	72.4	−	−
	Zhou et al. [44] (40–60 yr)	−	402	50	98	0.689
	Zhou et al. [44] (older than 60 yr)	−	223	81.3	98	0.585
Urine Bence−Jone protein
Urine Bence−Jone protein	Fan et al. [40]	73	114	64	−	−
Urine Bence−Jone protein and blood M protein	Fan et al. [40]	93	117	79.5	−	−
Radiological method
3D-STI diagnosis global circumferential strain
For GCS (Cut-off value = 16.09%)	Lei et al. [43]	49	52	94.23	87.5	0.927 (0.854–0.971)
For GAS (Cut-off value = 36.54%)	Lei et al. [43]	45	52	86.54	80	0.847 (0.757–0.914)
For GRS (Cut-off value = 31.90%)	Lei et al. [43]	42	52	80.8	47.5	0.664 (0.558–0.760)
Flow cytometry
Multiparametric flow cytometry (MFC) to measure the light chain restriction	Sa et al. [59]	96	119	80.70%

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Data availability statement

The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author.