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中华肾病研究电子杂志

中华肾病研究电子杂志 ›› 2023, Vol. 12 ›› Issue (02) : 67 -73. doi: 10.3877/cma.j.issn.2095-3216.2023.02.002

论著

轻链近端肾小管病超微病理特征及免疫电镜的诊断价值
侯晓涛1, 陈建雄2, 钟学军3, 岳书玲3, 王伶3, 杨惠霏4, 官阳5,†(), 周军2,†()   
  1. 1. 510515　广州，南方医科大学基础医学院病理学系；510515　广州，南方医科大学南方医院病理科；510005　广州，广州金域医学检验中心
    2. 510515　广州，南方医科大学基础医学院病理学系；510515　广州，南方医科大学南方医院病理科
    3. 510005　广州，广州金域医学检验中心
    4. 510063　广州，暨南大学附属复大肿瘤医院
    5. 430060　武汉，武汉大学人民医院超微病理中心
  • 收稿日期:2022-12-15 出版日期:2023-04-28
  • 通信作者: 官阳, 周军

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

Xiaotao Hou1, Jianxiong Chen2, Xuejun Zhong3, Shuling Yue3, Ling Wang3, Huifei Yang4, Yang Guan5,†(), Jun Zhou2,†()   

  1. 1. Department of Pathology, Southern Medical University School of Basic Medical Sciences, Guangzhou 510515, Guangdong Province; Department of Pathology, Nanfang Hospital of Southern Medical University, Guangzhou 510515, Guangdong Province; Guangzhou Kingmed Diagnostics Center, Guangzhou 510005, Guangdong Province
    2. Department of Pathology, Southern Medical University School of Basic Medical Sciences, Guangzhou 510515, Guangdong Province; Department of Pathology, Nanfang Hospital of Southern Medical University, Guangzhou 510515, Guangdong Province
    3. Guangzhou Kingmed Diagnostics Center, Guangzhou 510005, Guangdong Province
    4. Fuda Cancer Hospital Affiliated to Jinan University, Guangzhou 510063, Guangdong Province
    5. Ultrastructural Pathology Center, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province; China
  • Received:2022-12-15 Published:2023-04-28
  • Corresponding author: Yang Guan, Jun Zhou
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侯晓涛, 陈建雄, 钟学军, 岳书玲, 王伶, 杨惠霏, 官阳, 周军. 轻链近端肾小管病超微病理特征及免疫电镜的诊断价值[J]. 中华肾病研究电子杂志, 2023, 12(02): 67-73.

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.

目的

探讨轻链近端肾小管病(LCPT)的超微病理学特征及免疫电镜的诊断价值。

方法

选择本中心2018至2021年确诊或考虑轻链近端肾小管病病例140例，所有病例均进行免疫电镜检查，分析其超微病理特点，并探讨免疫电镜在轻链近端肾小管病诊断中的作用。

结果

病例以中老年为主，男性患者明显多于女性，所有病例均存在一定蛋白尿。这些LCPT患者的超微结构可分结晶型及非结晶型两大类，共5个形态学变异体。免疫病理分析，Kappa型轻链稍多，结晶型LCPT中，Kappa型占绝对优势，高达87.80%。免疫电镜在4种免疫病理检查方法中检出率最高，达94.29%。

结论

LCPT具有独特的超微病理表现，电镜及免疫电镜在LCPT诊断、分型及鉴别诊断上具有关键的作用，尤其在早期结晶型LCPT中。

关键词: 免疫电镜, 轻链, 近端小管病, 超微病理
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
表1 轻链近端肾小管病的临床和实验室检查特征
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)
表2 轻链近端肾小管病不同免疫病理方法单克隆轻链检出率[占比(%)]
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)
图1 轻链近端肾小管病超微结构特点(醋酸双氧铀、柠檬酸铅染色)注：A：胞质游离的结晶，×30 000；B：溶酶体内结晶，×40 000；C：淀粉纤维团，×30 000；D：粗大、束状纤维，×20 000；E：溶酶体消化不良，×3 000；F：溶酶体膜不完整，×20 000；G：巨大溶酶体，×15 000；H：边角锋利溶酶体，×15 000；I：溶酶体外排，×3 000
图2 轻链近端肾小管病鉴别诊断超微结构特点(醋酸双氧铀、柠檬酸铅染色)注：A：斑驳状溶酶体，×15 000；B：巨大、不规则溶酶体，×15 000；C：长条状、似结晶的巨大线粒体，×20 000；D：巨大、退变的线粒体，×30 000；E：细胞骨架聚集体，×30 000；F：自噬空泡，×6 000；G：过氧化物酶体(微体)，×30 000；H：溶酶体，免疫电镜溶菌酶标记×12 000
表3 轻链近端肾小管病超微病理特征及其免疫电镜标记情况与诊断推荐
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
表4 轻链近端肾小管病合并其它病理类型及轻链类型情况
合并类型 例数 Kappa[例(%)] Lambda[例(%)]
AL 20 9/20(45) 11/20(55)
CSH 4 4/4(100) 0
DN 7 5/7(71.43) 2/7(28.57)
IgAN 3 3/3(100) 0
MN 2 1/2(50) 1/2(50)
LCCN 26 12/26(46.15) 14/26(53.85)
足细胞病 2 2/2(100) 0
HCDD 1 0 1/1(100)
LCDD 2 2/2(100) 0
LCPD 6 6/6(100) 0
多部位 4 4/4(100) 0
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