Ultrastructural pathology features and diagnostic value of immunoelectron microscopy in light chain proximal tubulopathy

doi:10.3877/cma.j.issn.2095-3216.2023.02.002

Abstract

Abstract:

Objective

To investigate the ultrastructural pathology features and the diagnostic value of immunoelectron microscopy in light chain proximal tubulopathy (LCPT).

Methods

A total of 140 cases of LCPT confirmed or considered in our center from 2018 to 2021 were selected. All cases were examined by immunoelectron microscopy to analyze their ultrapathological characteristics and explore the role of immunoelectron microscopy in the diagnosis of LCPT.

Results

The patients were mainly middle-aged and elderly with the male patients being significantly more than the female. All the patients had proteinuria. The ultrastructure of these LCPT patients could be divided into crystalline and non-crystalline types, with a total of 5 morphological variants. Immunopathology analysis showed that kappa light chain was slightly more, and even predominated in crystalline LCPT (87.80%). The detection rate of immunoelectron microscopy was the highest among the four immunopathological examination methods (94.29%).

Conclusion

LCPT had unique ultrastructural pathology features. Electron microscopy and immunoelectron microscope may play an important role in the diagnosis、classification, and differential diagnosis of LCPT, especially of early crystalline LCPT.

Key words: Immunoelectron microscopy, Light chain, Proximal tubulopathy, Ultrastructural pathology

Xiaotao Hou, Jianxiong Chen, Xuejun Zhong, Shuling Yue, Ling Wang, Huifei Yang, Yang Guan, Jun Zhou. Ultrastructural pathology features and diagnostic value of immunoelectron microscopy in light chain proximal tubulopathy[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2023, 12(02): 67-73.

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Figures/Tables 6

References 20

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特征	所有病例(n＝140)	结晶型(n＝41)	非结晶型(n＝99)
年龄^a	59.56(58.00)	57.15(56.00)	60.56(61.00)
(范围)	(40~84)	(40~77)	(42~84)
男性[例(%)]	94(67.14)	29(70.73)	65(65.66)
血红蛋白^a	112.61(111.00)	122.00(116.00)	108.64(107.00)
(范围)	(50~318)	(72.0~318.0)	(50.0~162.0)
贫血[占比(%)]	52/111(46.85)	12/33(36.36)	40/78(51.28)
肌酐^a (μmol/L)	163.48(117.00)	156.19(128.15)	166.74(108.50)
(范围)	(35~1038)	(59.00~660.00)	(35~1038)
尿蛋白^a(g/24 h)	3.98(2.84)	3.47(2.43)	4.19(3.29)
<1 [占比(%)]	13/97(13.40)	4/29(13.79)	9/68(13.24)
1~3[占比(%)]	38/97(39.18)	15/29(51.72)	23/68(33.82)
>3[占比(%)]	46/97(47.42)	10/29(34.48)	36/68(52.94)
尿蛋白定性[占比(%)]
－	10/124(8.06)	4/36(11.11)	6/88(6.82)
1+	45/124(36.29)	12/36(33.33)	33/88(37.50)
2+	38/124(30.65)	8/36(22.22)	30/88(34.09)
3+及以上	31/124(25.00)	12/36(33.33)	19/88(21.59)
血浆白蛋白^a(g/L)	36.39(37.9)	38.77(38.90)	35.32(36.40)
(范围)	(14~51)	(24.00~51.00)	(14~49)

特征	所有病例(n＝140)	结晶型(n＝41)	非结晶型(n＝99)
年龄^a	59.56(58.00)	57.15(56.00)	60.56(61.00)
(范围)	(40~84)	(40~77)	(42~84)
男性[例(%)]	94(67.14)	29(70.73)	65(65.66)
血红蛋白^a	112.61(111.00)	122.00(116.00)	108.64(107.00)
(范围)	(50~318)	(72.0~318.0)	(50.0~162.0)
贫血[占比(%)]	52/111(46.85)	12/33(36.36)	40/78(51.28)
肌酐^a (μmol/L)	163.48(117.00)	156.19(128.15)	166.74(108.50)
(范围)	(35~1038)	(59.00~660.00)	(35~1038)
尿蛋白^a(g/24 h)	3.98(2.84)	3.47(2.43)	4.19(3.29)
<1 [占比(%)]	13/97(13.40)	4/29(13.79)	9/68(13.24)
1~3[占比(%)]	38/97(39.18)	15/29(51.72)	23/68(33.82)
>3[占比(%)]	46/97(47.42)	10/29(34.48)	36/68(52.94)
尿蛋白定性[占比(%)]
－	10/124(8.06)	4/36(11.11)	6/88(6.82)
1+	45/124(36.29)	12/36(33.33)	33/88(37.50)
2+	38/124(30.65)	8/36(22.22)	30/88(34.09)
3+及以上	31/124(25.00)	12/36(33.33)	19/88(21.59)
血浆白蛋白^a(g/L)	36.39(37.9)	38.77(38.90)	35.32(36.40)
(范围)	(14~51)	(24.00~51.00)	(14~49)

特征	所有病例(n＝140)	结晶型(n＝41)	非结晶型(n＝99)
冰冻荧光检出	43/136(31.62)	8/33(24.24)	35/103(33.98)
石蜡荧光检出	53/76(69.74)	17/29(58.62)	36/47(76.60)
免疫组化检出	49/53(92.45)	14/17(82.35)	35/36(97.22)
免疫电镜检出	132/140(94.29)	41/41(100)	91/99(91.92)

特征	所有病例(n＝140)	结晶型(n＝41)	非结晶型(n＝99)
冰冻荧光检出	43/136(31.62)	8/33(24.24)	35/103(33.98)
石蜡荧光检出	53/76(69.74)	17/29(58.62)	36/47(76.60)
免疫组化检出	49/53(92.45)	14/17(82.35)	35/36(97.22)
免疫电镜检出	132/140(94.29)	41/41(100)	91/99(91.92)

EM特征	特征描述	免疫电镜表达	诊断推荐
结晶	胞质游离(图1A)或膜包裹(图1B)。形态各样，杆状、多边形、菱形、不规则形	限制性表达，2~3+	符合
淀粉，纤维	淀粉纤维团(图1C)，膜包裹。纤维丝紊乱、无分支，直径约8~12 nm粗大、束状的纤维(图1D)，膜包裹或胞质游离直径不等	单一轻链限制性表达，2~3+	符合
溶酶体消化不良	溶酶体充满整个胞质，挤压核，胞质细胞器稀少，微绒毛多脱落，部分细胞崩解(图1E、图1F)	单一轻链限制性表达，2~3+	符合
溶酶体巨大异型化、边角锐利	增多、巨大、不规则、电子密度均一(图1G)边角锐利(图1H)	单一轻链限制性表达，2~3+	符合
溶酶体外排	部分小管上皮溶酶体明显增多、形态不规则、电子密度高且均一，细胞膜不完整，部分溶酶体外排至管腔(图1I)	单一轻链限制性表达，2~3+	高度怀疑
溶酶体斑驳状	电子密度不均、斑驳状(图2A)巨大、不规则，内含粗颗粒状电子致密物质，直径>1.2 μm(图2B)。上皮细胞溶酶体增多、但细胞无明显损伤	阴性或+/－	不考虑
巨大线粒体	长条状、似结晶(图2C)巨大化，部分含束状亚结构及内含物(图2D)	阴性	不考虑
细胞骨架聚集体	排列相较规则，微管、微丝、中间丝聚集，无膜包裹(图2E)，多在近肾小管基底膜侧分布	阴性	不考虑
自噬空泡	单层膜包裹，内含已被消化、电子密度较低的无定形物质(图2F)	阴性	不考虑
过氧化物酶体(微体)	直径0.1~0.5 m，形态各异，有包膜，内含细颗粒状基质，多含边缘板(图2)或核样体	阴性	不考虑
溶酶体	溶酶体吞噬大量溶菌酶(Lysozyme)，使上皮细胞呈现溶酶体消化不良形态	阴性	不考虑

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