IgG4-related hepatic inflammatory pseudotumour: could MRI suggest the correct diagnosis?

Abstract

We report a case of a 62-year-old woman, HIV positive, with a 3-week history of jaundice and elevated cholestatic enzymes. Imaging studies displayed intrahepatic biliary dilatation and a central liver lesion. Pathology described lesions of active cholangitis, lymphoplasmacytic infiltration and fibrosis, suggesting a hepatic inflammatory pseudotumour (IPT) IgG4 related. IgG4-related lymphoplasmacytic form of IPT belongs to IgG4-related diseases. We discuss the importance to include IgG4-related hepatic IPT as part of the differential diagnosis of any liver lesion, highlighting potential imaging clues that may help in establishing the correct diagnosis.

Background

Inflammatory pseudotumour (IPT) of the liver is a rare benign neoplasm that was first described in 1953.^{1 2} It was named therefore due to its propensity to clinically and radiologically mimic a malignant process.³

IPTs are now classified into two types based on the IgG4 stain: IgG4-related and non-IgG4 related.⁴ Few cases have been reported in the literature. The diagnosis is difficult as its imaging findings often resemble a malignant tumour.

Our case was initially misdiagnosed as a cholangiocarcinoma. In this article, we discuss some potential imaging clues that retrospectively would have helped to suspect an IPT in the first place.

Case presentation

A 62-year-old woman who was HIV positive came to our emergency department with a 3-week history of jaundice, choluria, acholia and mild abdominal pain. At physical examination she had right upper abdominal tenderness.

Laboratory findings depicted elevated aspartate aminotransferase: 128 U/L (reference value (RV): <32 U/L), alanine aminotransferase: 95 U/L (RV: <33 U/L), gamma glutamyl transferase: 627 U/L (RV: 6–42 U/L), alkaline phosphatase: 915 U/L (RV: 35–105 U/L), total bilirubin: 8.8 g/ dL (RV: <1.2 mg/dL) and direct bilirubin: 6.6 mg/dL (RV: <0.2 mg/dL). Tumour markers were negative: CA 19–9: 2.4 U/mL (RV: <37 UI/mL) and alpha fetoprotein 1.3 ng/mL (RV: <8 ng/mL).

Abdominal ultrasound showed intrahepatic biliary dilatation and diffuse thickening of the common bile duct (CBD) (figure 1).

Figure 1.

(A and B) Mild intrahepatic biliary dilatation without dilatation of the common bile duct. There was a central perihilar area, ill-defined, with heterogeneous echoes. The common bile duct showed diffuse parietal thickening which was dismissed at the onset (arrow in B).

Abdominal CT and MRI depicted a central hepatic mass causing secondary intrahepatic bile duct dilation. This lesion was isodense at arterial and portal venous phases, with late mild enhancement (figure 2). MRI showed mild hypointense signal in T1-weighted-image (WI), isointense signal in T2-WI, and mild delayed enhancement (figure 3).

Figure 2.

(A, B and C) Mild intrahepatic biliary dilatation with a central and isodense lesion, depicting mild late enhancement at the periphery of the lesion (C).

Figure 3.

The central liver mass is isointense in T1-WI (A) and T2-WI (B). Cholangiography sequence confirms the intrahepatic biliary dilatation with central abrupt cut-off lesion (C). T1-WI after gadolinium injection in arterial (D), portal venous (E) and delayed (F) phases depicts mild late capsule-like enhancement. WI, weighted-image.

The case was discussed at a multidisciplinary meeting which favoured the hypothesis of an intrahepatic cholangiocarcinoma or lymphoma. The patient was referred for a percutaneous needle biopsy.

Pathology described lesions of active cholangitis with lymphoplasmacytic infiltration and fibrosis. IgG4 immunostaining depicted 21 positive plasma cells per high-power field (HPF), which established the diagnosis of IPT IgG4 related (figure 4).

Figure 4.

(A) A proliferation of fibroblasts and inflammatory cells (mostly lymphocytes and plasma cells) around bile ducts. Immunohistochemistry (B) demonstrates plasma cells positive for anti-IgG4 antibody, confirming the diagnosis of inflammatory pseudotumour IgG4 related. H&E staining, 100× magnification.

Additional laboratory work-up revealed slight elevation of IgG 1760 mg/dL (RV: 700–1600 mg/dL) with normal serum IgG4 72.5 mg/dL (RV: 3–201 mg/dL).

Outcome and follow-up

Our patient underwent treatment with glucocorticoids (40 mg/daily) for 2 months and the lesion regressed completely on a follow-up CT scan after 3 months (figure 5). Biochemical parameters were completely normal in the third month of follow-up.

Figure 5.

Axial CT image, portal venous phase, 3 months after the onset, depicting complete imaging response.

The patient is being followed up for 2 years, without relapses or additional complications.

Discussion

IPT most commonly occurs in the lung, but may arise in nearly every system including the liver.⁵

The exact aetiology is unknown and possible causes include infection, autoimmune hepatobiliary diseases (IgG4 sclerosing cholangitis) and systemic granulomatous diseases (tuberculosis and sarcoidosis).⁶

Patients may be asymptomatic or present with non-specific symptoms such as fever, abdominal pain, weight loss and jaundice, which is secondary to obstruction of intrahepatic or extrahepatic bile ducts by the inflammatory mass.

According to Zen et al hepatic IPT may be categorised into two major pathological types: fibrohistiocytic and lymphoplasmacytic types. The fibrohistiocytic type is not IgG4 related, depict stromal fibrosis and fibroblastic proliferation, and trends to respond poorer to corticosteroid therapy.^{7 8} Instead, lymphoplasmacytic type, which was the case of our patient, is defined by an IgG4-positive plasma cell infiltration. Usually, the cut-off that has been accepted in literature to establish the diagnosis of IPT IgG4 related is above 10 HPF.^9–11

The imaging findings of both types of IPT are non-specific, as both can manifest as a single or multifocal mass. Nevertheless, the location usually differs, since lymphoplasmacytic type typically presents as a hilar lesion similar to periductal infiltrating-type hilar cholangiocarcinoma and the fibrohistiocytic type occurs mostly in the periphery of liver, as a mass-forming growth.⁵

The bile ducts adjacent and within IPT usually reveal cholangitis with periductal concentric and edematous fibrosis, resembling IgG4-related sclerosing cholangitis, and this typically affects primarily the extrahepatic ducts.⁸ This correlates with the diffuse parietal thickening of the CBD which was noted in our patient but was dismissed at the initial evaluation (figure 1B).

Laboratory tests are frequently normal, with slightly elevated liver enzymes and CA 19–9. Elevated serum IgG4 levels would have supported the diagnosis, however, it is known that up to 30% of the patients may have a normal serum concentration despite the histopathological criteria supporting a positive diagnosis.¹²

Imaging features are variable in the literature.4 5 13 14 The mass may be hypoattenuated or isoattenuated relative to muscle on unenhanced images. Enhancement is usually not pronounced, with variable enhancement patterns described. Delayed enhancement, particularly at the periphery of the lesion, which was present in our case, is considered to be typical of IPT. Although this feature is not specific, since cholangiocarcinoma or metastatic tumour may have the same enhancement pattern.¹⁵

Moreover, MRIs of hepatic IPT are not specific enough to differentiate IPT subtypes, that is to say IgG4-related IPT from non-IgG4-related IPT. Interestingly, most IPTs, regardless of the subtype, show isointensity in T2-WI, which was the case of our patient. Isointensity in T2-WI would stand out against other differential diagnoses that were considered, such as liver lymphoma and cholangiocarcinoma, both of which usually demonstrate hyperintense signal in T2-WI. On the other hand, lymphomas do not usually cause biliary dilatation. AIDS-associated cholangiopathy was considered unlikely since the CD4 count was normal (>1000 cells/mm³).

A biopsy is crucial to allow a definitive diagnosis. Despite the benign nature of IPT, some authors reported their recurrence and potential of malignant transformation. Inflammatory myofibroblastic tumour is the possible counterpart of IPT, however the rate of malignant degeneration is unknown.⁹ According to literature, local recurrence may developed in 25% of cases.¹⁶

Thus, the treatment still remains controversial in the literature. The conservative treatment with glucocorticoids is usually first tempted. If it fails, surgery may be necessary.¹³

Learning points.

• Inflammatory pseudotumour (IPT) is a very rare condition and mimics malignant tumours. It is associated with infectious, inflammatory and autoimmune diseases, such as IgG4-related diseases.

• MRI may be helpful as IPTs may demonstrate isointense signal in T2-weighted-image (WI). Instead most hepatic malignancies are hyperintense in T2-WI. After contrast, delayed enhancement at the periphery of the lesion is described as a characteristic feature of IPT.

• Marked thickening of the extrahepatic bile duct favours the diagnosis of IgG4-related cholangiopathy.

• IPT should be kept in mind as part of differential diagnosis of liver masses. Though MRI may be helpful, histopathology and immunohistochemical studies are mandatory to establish the diagnosis of IPT.

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