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SCIENCE CHINA Life Sciences, Volume 63 , Issue 5 : 764-770(2020) https://doi.org/10.1007/s11427-019-9539-6

Clinical strategies for differentiating IgG4-related cholecystitis from gallbladder carcinoma to avoid unnecessary surgical resection

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  • ReceivedMar 16, 2019
  • AcceptedApr 22, 2019
  • PublishedJul 17, 2019

Abstract

Immunoglobulin G4 (IgG4)-related cholecystitis (IgG4-C) is often difficult to distinguish from gallbladder carcinoma (GBC). This study aimed to determine a practical strategy for differentiating between IgG4-C and GBC to avoid unnecessary surgical resection. The expression of IgG4 in the gallbladder was detected by immunohistochemistry. The clinicopathological and radiological characteristics of IgG4-C patients and GBC patients were analyzed retrospectively. Immunohistochemistry revealed that IgG4 was upregulated in the plasma cells of IgG4-C tissues. The median serum total bilirubin levels were significantly higher in the patients with IgG4-C than in those with GBC (45.8 µmol L−1 vs. 29.9 µmol L−1). The serum γ-GGT levels were higher in IgG4-C patients than in GBC patients, whereas the serum levels of CA125 were significantly higher in GBC patients than in IgG4-C patients. The imaging scans were helpful for differentiating IgG4-C from GBC based on the presence of a layered pattern and Rokitansky-Aschoff sinuses in the gallbladder wall. There were no statistically significant differences in age, presence of abdominal pain, level of emaciation between the two groups. Our study demonstrated that the combination of imaging with serum total bilirubin, γ-GGT and CA125 levels can offer added preoperative diagnostic value and reduce the rate of IgG4-C misdiagnosis.


Funded by

the Special Research Foundation of the National Nature Science Foundation of China(81301865,81672412,81772597,81702904)

the Guandong Natural Science Foundation(2016A030313840,2017A030311002,2018A030313645)

Science and Technology Program of Guangzhou

China(201607010111)

Pearl River S&T Nova Program of Guangzhou

China(201610010022)

the Fundamental Research Funds for the Central Universities(18ykpy22)

Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology([2013]163)

the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes(KLB09001)

Guangdong Science and Technology Department(2015B050501004,2017B030314026)


Acknowledgment

This work was supported by the Special Research Foundation of the National Nature Science Foundation of China (81301865, 81672412, 81772597 and 81702904), the Guandong Natural Science Foundation (2016A030313840, 2017A030311002 and 2018A030313645 ); the Guangdong Science and Technology Foundation (2016A020215199 and 2017A020215196), Science and Technology Program of Guangzhou, China (201607010111), Pearl River S&T Nova Program of Guangzhou, China (201610010022), the Fundamental Research Funds for the Central Universities (18ykpy22), Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology ([2013]163), the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes (KLB09001), Guangdong Science and Technology Department (2015B050501004, 2017B030314026).


Interest statement

The author(s) declare that they have no conflict of interest.


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  • Figure 1

    The expression of IgG4 is upregulated in IgG4-C tissues. IgG4-C tissues (n=21) and GBC tissues (n=41) were fixed in formalin and embedded in paraffin. IgG4 was stained using immunohistochemistry. The results revealed positive staining of IgG4 proteins (black arrow) in the plasma cells of IgG4-C tissues (A, ×200 magnification and B, ×400 magnification). IgG4 was not expressed in GBC tissues (C, ×200 magnification and D, ×400 magnification).The difference in expression was significant (P<0.05).

  • Figure 2

    Macroscopic findings from the 21 IgG4-C tissue samples. IgG4-C tissues were routinely stained with H&E staining. The results demonstrated marked fibrosis in the IgG4-C tissues (A, red arrow, ×200). The plasma cells (B, black arrow, ×200 magnification) and lymphocytes (B, blue arrow, ×100 magnification) infiltrated the IgG4-C tissues.

  • Figure 3

    Radiological differences between IgG4-C and GBC. The imaging features of IgG4-C (A–D) and GBC (E–H) patients. The MR scanrevealed diffuse intermediate signal intensity of the gallbladder wall with “Rokitanskye-Aschoff sinuses” sign change (white arrow). A, sagittal T2-weighted image (T2WI); B, sagittal T1-weighted image (T1WI)) and diffuse gallbladder wall thickening in IgG4-C patients (C, white arrow). The CT scan revealed an infiltrative low-density mass involving the body portion of the adjacent hepatic parenchyma (D, black arrow). In GBC patients, we did not observe see “Rokitanskye-Aschoff sinuses” sign change in the gallbladder wall (E, white arrow), and the thickening of the gallbladder wall had no layered patternord is continuous enhancement of the mucosal wall (F, black arrow). GBC patients had lower enhancement of the nodules in the portal phase, which was not observed in IgG4-C patients (G, black arrow). Metastases might be observed in GBC patients (H, black arrow).

  • Figure 4

    (Color online) Clinical strategies for distinguishing IgG4-C from GBC to avoid unnecessary surgical resection based on our study.

  • Table 1   Clinicopathologic data of the IgG4-C and GBC patients

    Characteristics

    N

    IgG4-C patients

    GBC patients

    P value*

    Sex

    0.621

    Male

    36

    16

    20

     

    Female

    26

    5

    21

     

    Age (years)

    0.518

    ≤50

    8

    4

    4

     

    >50

    54

    17

    37

     

    IgG4

    0.001

    Positive

    21

    21

    0

     

    Negative

    41

    0

    41

     

    Abdominal pain

    0.372

    Yes

    38

    15

    23

     

    No

    24

    6

    18

     

    Jaundice

    0.004

    Yes

    20

    15

    5

     

    No

    42

    6

    36

     

    Emaciation

    0.220

    Yes

    29

    8

    21

     

    No

    33

    13

    20

     

    Gallbladder stone

    0.174

    Yes

    20

    6

    14

     

    No

    42

    15

    27

     

    Cholangiolithiasis

    0.089

    Yes

    27

    14

    13

     

    No

    35

    7

    28

     

    Serum total bilirubin

    0.001

    ≤40 μmol L−1

    40

    6

    34

     

    >40 μmol L−1

    22

    15

    7

     

    Serum γ-GGT

    0.004

    ≤50 U L−1

    28

    4

    24

     

    >50 U L−1

    34

    17

    17

     

    Serum AFP

    0.314

    ≤25 ng mL−1

    56

    19

    37

     

    >25 ng mL−1

    6

    2

    4

     

    Serum CEA

    0.102

    ≤5 μg L−1

    48

    20

    28

     

    >5 μg L−1

    14

    1

    13

     

    Serum CA125

    0.017

    ≤35 U mL−1

    30

    17

    13

     

    >35 U mL−1

    32

    4

    28

     

    Serum CA199

    0.317

    ≤37 U mL−1

    34

    14

    20

     

    >37 U mL−1

    28

    7

    21

     

    AFP=alpha-fetoprotein. *: Compared via the chi-square test (Fisher’s exact test)

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