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. 2023 Aug 24;15(8):e44066. doi: 10.7759/cureus.44066

Incidental Finding of Hepatic Inflammatory Pseudotumor Immunoglobulin G4-Related Disease With Underlying Chronic Hepatitis C

Malique Delbrune 1,✉, Nicha Wongjarupong 1, Elizabeth S Aby 2, Carlos Iwamoto 3, Mohamed Hassan 1
Editors: Alexander Muacevic, John R Adler
PMCID: PMC10517879  PMID: 37750140

Abstract

Immunoglobulin G4-related disease (IgG4-RD) is a unique immunological disease that can impact multiple organs including a formation of a hepatic inflammatory pseudotumor (IPT). We present a case of a 67-year-old male with a history of chronic viral hepatitis C infection who had an accidental finding on magnetic resonance imaging (MRI) of a liver arterially enhancing lesion. With an extensive work-up, immunohistochemical stains for immunoglobulin G of the liver lesion was performed and showed markedly increased IgG4-positive plasma cells (> 50/HPF), which was consistent with hepatic inflammatory pseudotumor related to IgG4-RD. The patient was treated with prednisone with a complete resolution of the hepatic lesion. The diagnosis of hepatic IPT and IgG4-RD requires a high degree of clinical suspicion and coordination with a multi-disciplinary team, including pathologists. Early tissue acquisition and staining for IgG4 was essential for the early diagnosis and treatment in this case. We also provide a comprehensive summary of published reports of IgG4-RD presenting with IPT.

Keywords: case report, gastroenterology, igg4 -related disease, hepatic pseudotumor, chronic hepatitis c virus

Introduction

Immunoglobulin G4-related disease (IgG4-RD) is an immune mediated condition that can affect multiple organs and lead to organ failure [1]. The presentation of IgG4-RD can vary from asymptomatic to subacute multi organ failure; on occasion patients can present with mass-like lesions, which can be concerning for malignancy [1]. IgG4 related inflammatory pseudotumor (IPT) presenting in the liver is a rare manifestation of IgG4-RD with few cases described [2]. Hepatic IPTs make up roughly 8% of lesions associated with IgG4-RD [3]. We present a patient with history of laparoscopic cholecystectomy complicated by common hepatic artery transection and damage to the confluence of right anterior and left hepatic ducts and chronic hepatitis C with incidental finding of hepatic IPT confirmed on liver biopsy.

Case presentation

A 67-year-old male with a history of chronic viral hepatitis C (with a sustained virologic response following treatment with velpatasvir-sofobuvir and ribavirin seven years prior) without advanced hepatic fibrosis presented with a bile duct injury following laparoscopic cholecystectomy for symptomatic acute cholecystitis. His post operative course was complicated by multiple instances in which percutaneous drains placed at the time of surgery were dislodged and during one drain replacement, the tube was passed through the hepatic venous system and pleural space with subsequent bilo-thorax development. Magnetic resonance imaging (MRI) for drain assessment found an enlarging arterially enhancing lesion involving hepatic segment 3, measuring 2 cm, with associated washout and pseudo capsule, concerning for hepatocellular carcinoma (HCC) (Figure 1). His laboratory values at that time were alkaline phosphatase 263 U/L (40-129 U/L), aspartate aminotransferase (AST) 78 U/L (10-50), alanine aminotransferase (ALT) 102 U/L (10-50), total bilirubin 0.7 mg/dL (<1.2 mg/dL), direct bilirubin 0.29 mg/dL (0-0.30 mg/dL), international normalized ratio (INR) 1.28 (0.85-1.15), and serum creatinine 1.39 mg/dL (0.67-1.17 mg/dL).

Figure 1. MRI image .

Figure 1

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Magnetic resonance imaging (MRI) revealed an arterially enhancing lesion arising exophytically in segment III of the liver with associated washout and pseudocapsule (red arrow).

A core needle biopsy of the liver lesion was performed and showed an inflammatory process composed of abundant lymphoplasmacytic inflammation with focal storiform-type fibrosis. Immunohistochemical stains for Immunoglobulin G (IgG) performed showed markedly increased IgG4 positive plasma cells (> 50/HPF), which was consistent with IgG4-RD. Alpha-fetoprotein collected two months prior was 4 ng/mL (<8.3 ng/mL). Immunological staining of the patient’s gallbladder from his prior cholecystectomy did not demonstrate an elevated IgG4 to IgG plasma cell ratio suggesting IgG4-RD in the gallbladder.

The patient was started on a prednisone taper plan as follows: 40 mg for 14 days, then 20 mg for 14 days, and then 10 mg for 14 days. Following the first two-week course of steroid treatment, his laboratory studies were as follows: alkaline phosphatase 125 U/L (40-126 U/L), AST 38 U/L (10-50 U/L), ALT 57 U/L (10-50 U/L), total bilirubin 0.5 mg/dL (<1.2mg/dL), direct bilirubin 0.28 mg/dL (0.0-0.30 mg/dL), INR 1.41 (0.85-1.15), and serum creatinine 2.56 mg/dL (0.67-1.17 mg/dL). After the patient had completed the steroid treatment plan, follow-up imaging was done. The visualized mass-like structure was not visualized on magnetic resonance cholangiopancreatography (MRCP) (Figure 2). The serum IgG4 level collected after the steroid treatment, which was three months following the diagnosis, was 34 mg/dL (4-86 mg/dL).

Figure 2. Follow-up MRCP imaging.

Figure 2

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Magnetic resonance cholangiopancreatography (MRCP) image demonstrating lack of visualization of a previously noted lesion in segment III of the liver.

Discussion

Hepatic IPT is a rare benign tumor that can mimic liver cancer, such as HCC, on imaging. When evaluating hepatic lesions, cross-sectional imaging such as MRI and computerized tomography (CT) are often unable to differentiate concerns for malignancy from IgG4-RD. In the presenting case, there was a high suspicion of HCC because the lesion was exophytic, had enhancement on imaging, and the patient had a history of hepatitis C, although the patient had no evidence of advanced fibrosis. The diagnosis of IgG4-RD can be made clinically using the Japanese Comprehensive Clinical Diagnostic (CCD) criteria for IgG4-RD and histopathology [4]. The Japanese CCD 2011 criteria for IgG4-RD are as follows: organ involvement, such as diffuse/localized swelling; elevated serum IgG4 concentrations > 135 mg/dl; and marked plasmacyte infiltration, defined as >10 IgG4+ cells per high-powered field (HPF) and a > 40% ratio of IgG4+/IgG + cells, accompanied by fibrosis on histopathological examination [4]. The criteria for IgG4-RD was updated in 2020 by the original Japanese IgG4-RD team with the following change to clinical presentation: clinical and radiological features of one or more organs showing diffuse or localized swelling or a mass or nodule characteristic of IgG4-RD and in single organ involvement, lymph node swelling is omitted [4]. Laboratory findings of IgG4 serum concentration greater than 140 mg/dL are seen in more than 70% of patients and elevation at least two times the upper limit of 140 mg/dL is 99% specific for IgG4-RD [5].

The patient did not obtain a serum IgG4 level until after steroid treatment and at that time, serum IgG4 levels were found to be within normal limits. A biopsy is essential to make the definitive diagnosis of IgG4-RD. The pathognomonic histology for IgG4-RD includes a dense lymphoplasmacytic infiltrate with a storiform pattern, evidence of obliterative phlebitis, and moderate eosinophilic infiltrate that is positive for IgG4 plasma cells; a diagnosis requires two out of three findings [1,6,7]. The patient’s liver biopsy met these diagnostic criteria. There is a concern for seeding of the malignancy during a biopsy; seeding has been seen in 2.7% of cases following the biopsy of a malignant liver tumor [8]. If the etiology of the mass is unclear following biopsy and there is a high suspicion of malignancy, surgical resection can be performed. Treatment for IgG4-RD relies on steroids or other immunosuppressants. The current recommendation for treatment includes four weeks of prednisone at a dose of 30-40 mg daily with a taper every two weeks of 5 mg or 0.6 mg/kg every 2-4 weeks over 3-6 months [1,9]. Some cases have been shown to resolve spontaneously without steroid treatment at 1-year follow-up [3,10].

A literature search via PubMed using key terms -IgG4, -hepatic, and -pseudotumor found 38 case reports. After excluding cases without access to full text (n= 18) and patients of <18 years old (n= 1), 19 case reports remained (Table 1). The mean age of presentation was 60.7 years. The majority of Ig4-related liver diseases occurred in males (84%). A common factor amongst cases was that imaging findings were inconclusive in determining if the etiology was malignant or infectious. Ten of the 19 cases reviewed provided serum IgG4 levels, 70% (7/10) of the cases did not meet the serum IgG4 levels proposed by Nambiar and Oliver [5], which were proposed to be 99% specific for the diagnosis of IgG4-RD. Of all the papers found, there were no other case reports involving a patient with hepatic pseudotumor from IgG4-RD and a history of hepatitis C. The association between hepatitis C and IgG4-RD is currently unknown. One potential mechanism for the relationship is that immunoglobulins, such as IgG4, play a role in the disease course of both conditions. One study proposed that in hepatitis C infections, the presence of IgG4 antibodies was correlated with lower levels of viremia [11]. However, further study is needed to determine the link between IgG4 levels, IgG4-RD and hepatitis C.

Table 1. Review of published case reports of hepatic pseudotumor IgG4-RD.

Article Age Sex Tumor Location Biopsy Biopsy Method Resection Initial Diagnostic Impression Serum IgG4 Imaging Diagnosis Criteria Previous malignancy Treatment History of Hepatitis C
Jandee and Boonsrib, 2020 [12] 50 Male Hepatic segment 5 Yes Ultrasound-guided liver biopsy No Parasitic infection,chronic abscess 5330 mg/dL Abdominal CT, MRI Serum immunoglobulin No Steroid (prednisolone 40mg/day) Azathioprine 50mg/day for maintenance after 3 months of starting steroid No
Shibata et al., 2016 [8] 72 Male Hepatic segment 7 Yes Ultrasound using 18 gauge needle No   137 mg/dL CT   Yes, Hilar cholangiocarcinoma and bile duct carcinoma Antibiotics initially due to diabetes, nsaids and ursodeoxycholic acid. Symptoms persisted so steroids started no
Legkiy et al., 2017 [13] 60 Male Hepatic segments 2 and 6 Yes Ultrasound guided percutaneous needle biopsy No    Did not quantify CT   IgG4 levels serum of 19.1g/l     No
Yoon et al., 2022 [9]  59 Male Hepatic hilum unspecified segment Yes CT-guided biopsy No   354 mg/dL   Elevated IgG4, histology No Prednisone no
Miyagi et al., 2022  [3] 66 Male Hepatic segment 4 Yes ultrasonography-guided puncture No   Elevated, specific value not given CT imaging Immunoglobulin level No No antibiotics after MRCP draining stones in bile duct, inflammation improved No
Hamano et al., 2021 [6] 71 Male Hepatic segment 3 Yes Ultrasound Guigui biopsy No Intrahepatic cholangiocarcinoma  205 mg/DL (5-117 mg/dL) Abdominal CT initially, MMRI   IgG4 RD Renal disease 10mg prednisone daily No
Naitoh et al., 2009 [14] 77 Male Hepatic segment 3 No No Yes, left lobectomy Intrahepatic cholangiocarcinoma  231 mg/DL (normal <134 mg/dL) CT imaging, MRI, MRCP, ERCP   No Surgical Resection No
Kaneko et al., 2017 [15] 73 Male Left lobe of liver mass unspecified segment Yes Ultrasound guided biopsy No Hepatic IPT, DLBCL Elevated, specific value not given CT imaging   Pancreatic head mass cancer R-CHOP chemotherapy for Diffuse large b-cell lymphoma on liver, No
Lee et al., 2018 [2] 67 Male Right hepatic lobe unspecified segment NO No Yes,Resection of right lower lobe Sarcomatous intrahepatic cholangiocarcinoma Did not assess before removal CT imaging, MRI     Surgical resection done No
Kim et al., 2011 [16]  58 Male Along the left portal vein unspecified Yes Percutaneous biopsy   IgG4 and malignant lymphoma Elevated, specific value not given CT imaging Biopsy showing elevated IgG4 staining No 30 mg prednisone No
Patel et al., 2018 [10]  48 Male Right lobe of liver unspecified Yes Did not specify No Chronic pancreatitis causing inflammation 114 mg/dL CT imaging, MRI Pathology None None No
Primitivo et al., 2021 [17]  62 Female Central liver mass Yes Percutaneous needle No Did not state non elevated 72.5 mg/dL Ultrasound, CT Pathology showing active cholangitis with lymphoplasmacytic infiltration and fibrosis None, HIV positive glucocorticoids 40mg No
Koiwai et al., 2021 [18]  71 Male Liver hilum Yes Ultrasound guided fine needle biopsy No Did not state 465 mg/dL CT imaging, MRCP   Pancreatic head tumor Prednisone 0.6mg/kg No
Miyajima et al., 2017 [19]  50 Female Lateral lobe unspecified Yes Unspecified No Cholangiocellular carcinoma, hepatocellular carcinoma, metastatic liver tumor, actinomycosis 241 mg/dL Ultrasound, CT Elevated serum IgG4, random samplings showing elevated plasma cells No Antibiotics initially, prednisolone 0.5mg/kg No, Hepatitis C antibodies negative
Kanno et al., 2005 [20] 48 Male Left hepatic lobe unspecified segment No No Left lobectomy Autoimmune pancreatitis with multiple metastatic liver tumors from cholangiocellular carcinoma   Ultrasound, CT, ERCP Histology showing diffuse and dense lymphoplasmacytic infiltration with obliterating phlebitis None Corticosteroid treatment No
Mulki et al., 2015 [7]  50 Male Right lobe of liver unspecified segment Yes Ultrasound guided No Multifocal necrotic hepatic abscesses with septic thrombus, possible malignancy   Ultrasound, CT   No Antibiotics initially, did not start immunotherapy because patient was asymptomatic No
Uchida et al., 2007 [21]  54 Male Hepatic segment IV Yes Did not state No Pancreatic cancer with metastasis   Ultrasound, CT Biopsy pathology No None, resolved on its own, patient was asymptomatic No, Hepatitis C antibodies negative
Okamura et al., 2021 [22]  67 Male Left umbilical tumor No did not biopsy Yes Intrahepatic cholangiocarcinoma 206 mg/dL MRI Histology IgG4 Sclerosing cholangitis   No
Agaimy and Märkl, 2013 [23] 51 Female Hepatic segments II/IV No No Yes Infectious etiology, AML No serum IgG4 level CT, Ultrasound Histology status post resection   Surgical removal, symptoms resolved so no other intervention No
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Conclusions

We incidentally discovered a patient with IgG4-RD with the presentation of hepatic IPT. The diagnosis of hepatic IPT and IgG4-RD requires a high degree of clinical suspicion and coordination with a multi-disciplinary team, including pathologists. The Japanese CCD criteria can be used to determine the probability of the diagnosis. In cases such as this one, serum IgG4 levels may not be drawn prior to treatment. However, it is reassuring to see normal serum IgG4 levels following steroid treatment. Early tissue acquisition and staining for IgG4 was essential for the early diagnosis and treatment in this case. Comparing this patient’s case with previously published case reports of hepatic IPT, the patient’s chronic hepatitis C was found to be unique. The exact mechanism connecting hepatitis C and IgG4-RD is still unknown requiring further study with levels of IgG4 immunoglobulin influencing each disease's progression. Our patient completed steroid treatment and follow-up imaging did not visualize the previously demonstrated mass.

The authors have declared that no competing interests exist.

Human Ethics

Consent was obtained or waived by all participants in this study

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