Introduction
Inflammatory pseudotumor (IPT) is a rare benign lesion of unknown origin, characterized
by proliferation of fibrous connective tissue and invasion of inflammatory cells.
Etiology remains uncertain although various theories including infection, autoimmune
disease, systemic inflammatory response, trauma, and neoplasm have been postulated.
It has been reported at various sites in the body, with the lung and liver being the
most common. It is important to recognize this as a distinct entity as it can have
a variable appearance on imaging and mimic a malignant mass.
We present a case of hepatic IPT with variable interpretation on different imaging
modalities. The lesion was prospectively diagnosed as neoplasm on ultrasound, abscess
on computed tomography (CT), and complex cystic neoplasm (biliary cystadenoma) on
magnetic resonance imaging (MRI).
Case Presentation
A 33-year-old African American woman, with no significant past medical history, presented
to emergency room with abdominal pain and distension for 6 weeks and fever, chills,
nausea, vomiting, and jaundice for 2 weeks.
Review of systems showed no fever or chills and no costophrenic tenderness or shortness
of breath with tenderness in the right upper quadrant of the abdomen. There was no
weight loss or loss of appetite. Laboratory studies revealed elevated white blood
count (WBC) at 21.1 and decreased hemoglobin at 9.2. Neutrophils, lymphocytes, and
monocytes were elevated. Serum alkaline phosphatase, bilirubin, and aminotransferases
were within normal limits. Serum α-fetoprotein was normal.
Ultrasound demonstrated a complex mass in the left hepatic lobe measuring 12.8 × 6.0
cm in biaxial dimensions with a heterogenous and echogenic appearance. Vascularity
in the septae was seen on color Doppler imaging. Sonographic features were not typical
of an abscess ([Fig. 1]) and suggestive of a mixed solid, cystic neoplasm.
Fig. 1 Ultrasound of liver demonstrates a large oval-shaped mass with well-defined margins
in left lobe involving segments II and III with mixed solid and cystic components
(arrows).
To further characterize the lesion, CT of the abdomen and pelvis with oral and intravenous
contrast (Omnipaque 350) was performed, and it showed acute noncomplicated diverticulitis
of the sigmoid colon. Corresponding to the sonographic abnormality, there was a complex
multiloculated lesion in the left lobe of the liver with a mean attenuation value
of 42 Hounsfield units on portal-venous phase. The lesion demonstrated peripheral
rim enhancement as well as enhancing internal septations ([Fig. 2A, B]). This was interpreted as a liver abscess given the coexisting sigmoid diverticulitis.
Fig. 2 (A) Computed tomography (CT) of the abdomen and pelvis in portal-venous phase shows a
hypodense well-circumscribed mass in left lobe of liver with rim enhancement and mild
internal septal enhancement (arrows). Inflamed segment of bowel secondary to diverticulitis
in lower abdomen (star). (B) Delayed phase CT scan shows increased enhancement of the septations.
MRI was performed on a 1.5 Tesla Phillips magnet with intravenous administration of
13 mL Dotarem (gadoterate meglumine). It demonstrated a multiloculated, 9.0 × 3.0
× 5.7-cm lesion spanning segments II and III that was heterogeneously hyperintense
on T2-weighted imaging with scattered cystic areas ([Fig. 3A]) and predominantly hypointense on T1-weighted imaging ([Fig. 3B]). Few foci of increased T1 hyperintensity noted within the lesion were presumed
to be foci of hemorrhage. Restricted diffusion was noted ([Fig. 4A, B]). Peripheral rim enhancement as well as enhancement of internal septations was noted
on administration of intravenous gadolinium with only mild peripheral hyperemia in
the surrounding liver ([Fig. 5A–C]). The internal septae enhanced almost equal to or some even more than the adjacent
hepatic parenchyma. Differential diagnosis considered was complex biliary cystic lesion
such as a biliary cystadenoma or cystadenocarcinoma rather than an atypical abscess,
given the fact that a large pyogenic abscess would elicit marked adjacent hyperemia,
entail destruction of hepatic parenchyma, and not demonstrate internal enhancement.
Fig. 3 (A) Axial T2-weighted MRI demonstrates a well-circumscribed hyperintense lesion involving
segments II and III of liver with few scattered cystic areas (arrows). (B) Lesion is hypointense on T1-weighted sequences. Few foci of T1 hyperintensity presumed
secondary to intralesional hemorrhage.
Fig. 4 (A, B) Restricted diffusion noted in the lesion on diffusion-weighted imaging with hyperintense
signal on high b-value sequences and hypointensity on corresponding ADC maps.
Fig. 5 (A) Postcontrast axial T1-weighted imaging shows mild peripheral and septal enhancement
on the arterial phase following administration of intravenous gadolinium. (B, C) Progressive and gradual internal septal enhancement noted on the portal-venous and
delayed phases of postcontrast imaging.
The patient was referred to surgical oncology due to indeterminate etiology and atypical
imaging characteristics, and a left hepatectomy was performed. On gross examination,
a solid-appearing abnormal area was seen in the left lobe of the liver. Microscopically
the abnormality was characterized by thick fibrous septae haphazardly separating regions
of foamy as well as pigment-laden macrophages. There was abundant lymphoplasmacytic
infiltration. Immunoglobulin G (IgG) stain showed numerous plasma cells, and IgG4
was positive in only 10% of the IgG-positive plasma cells (not consistent with IgG4-related
disease). Background liver parenchyma surrounding the lesion demonstrated no significant
histopathologic change ([Fig. 6A, B]).
Fig. 6 Two microscopic images from a representative H&E stain. (A) A 10 × objective (lower power) showing inflammatory cells infiltrating a fibrous
stroma. (B) 40 × objective (higher power) highlighting the inflammatory infiltrate that consists
predominantly of plasma cells (polytypic by kappa and lambda in situ hybridization
stains) and macrophages containing brown yellow pigment. (Image courtesy: Dr. Kari
Caradine, Department of Pathology, University of Arkansas for Medical Sciences.)
Discussion
IPT is a rare entity, consisting of proliferating fibrous tissue infiltrated by inflammatory
cells. It can develop in several organs, such as the brain, spinal cord, thyroid,
breast, pancreas, urinary bladder, gastrointestinal tract, and lungs, but it is most
common in the lungs and liver. The exact pathogenesis is still unclear, but some studies
consider it as a host immunologic response to chronic stimulation by pathogenic microorganisms,
neoplasm, pregnancy, or immune system disease. The lesion is often single, consisting
mainly of proliferation of connective tissue and invasion of inflammatory cells, often
with fat deposition, necrosis, and bleeding. There is a great histologic variation
in the composition of IPT reflected in the numerous terms that have been used to describe
them, including inflammatory myofibroblastic tumor, plasma cell granuloma, histiocytoma,
and fibroxanthoma.[1]
[2]
Many of the features of IPT can be related to the production of inflammatory mediators
such as cytokines and particularly interleukin-1. Locally, interleukin-1 stimulates
the proliferation of fibroblasts, extravasation of neutrophils, and the activation
and increase of procoagulant activity of vascular endothelium. Some authors believe
this tumor is a low-grade fibrosarcoma with inflammatory (lymphomatous) cells. It
has also been suggested that histiocytic cells predominate in IPTs associated with
infection, whereas myofibroblastic cells characterize the lesions more likely to be
considered true neoplasms.[1]
IPT of the liver was first described by Pack and Baker in 1953. It is more common
in the right lobe of the liver, and though benign, it may mimic malignancy.[3] Previous studies from Western countries reported that IPT of the liver is common
in men of mid-thirties. In contrast, patients from Eastern countries tend to show
older age of onset. Males of non-European background are predominantly affected, with
a reported male-to-female ratio ranging from 3:1 up to 8:1.
Hepatic IPT is most commonly described as a well-defined and solitary intrahepatic
tumor in the right lobe. Multifocal tumors, concurrent hepatic and splenic IPT, and
portal vein occlusion have also been reported. Larger lesions may undergo central
necrosis. Short interval imaging follow-up may reveal a decrease in the size of lesion
suggesting its benignity,[4] with a few studies also reporting spontaneous regression.[5]
Clinical and laboratory findings are nonspecific, with the most common presenting
symptoms being fever, epigastric pain, malaise, and weight loss. Other findings may
include obstructive jaundice, hepatomegaly, splenomegaly, and portal hypertension.[2] Laboratory findings may suggest an inflammatory process with marked leukocytosis,
elevated erythrocyte sedimentation rate, and C-reactive protein. Anemia, thrombocytosis,
and elevated IgG levels have also been reported.[2]
[4]
[5]
On ultrasound, hepatic IPT demonstrates variable echogenicity. Hypoechoic appearance
is more common, but hyperechoic and complex lesions have also been described.[6] Previously, a study using contrast-enhanced ultrasound postulated that pseudotumors
demonstrated lack of enhancement in all phases of contrast. A recent study using contrast-enhanced
ultrasound has reported that “fast-in and centrifugal-out” pattern of enhancement
may be a characteristic pattern in the diagnosis of these lesions. After contrast
agent injection, all these lesions showed a fast-in and fast-out enhancement pattern,
with hyperenhancement in the early arterial phase and centrifugal washout in the late
arterial or early portal-venous phase. The centrifugal washout showed the highest
diagnostic ability in differentiating a hepatic IPT from hepatocellular carcinoma,
which demonstrates rapid washout with a hypoechoic appearance.[7]
CT findings of IPT are very variable. Hypoattenuating ill-defined masses with varying
degrees of contrast enhancement are the most common. Delayed enhancement, especially
septal and peripheral, can be seen and is thought to be related to fibrous components.[4]
[5]
MRI findings of hepatic IPTs are also variable. Hypointense signal relative to the
liver on T1-weighted imaging and isointense to hyperintense signal on T2-weighted
imaging is common, although iso- and hyperintense lesions on T1 have also been described.[5] Peripheral and septal enhancements are commonly described after gadolinium administration,
secondary to the fibrous components.
Studies that compared the differences of CT and MRI in their diagnostic accuracy for
hepatic IPTs concluded that both examination techniques are comparable, and when IPT
is being suspected, there is no advantage of combining CT and MRI techniques or using
one over the other to obtain a more conclusive diagnosis. They showed an obvious superiority
of CT and MRI over ultrasound in terms of diagnostic conclusiveness.[8]
Histopathologic confirmation via percutaneous biopsy or following surgical resection
is often necessary to differentiate from other hepatic lesions such as malignant tumors
and non-liquefied abscesses. The key to differentiate IPTs from abscesses, especially
in the presence of cystic or necrotic components, is the replacement of hepatic parenchyma
with collagenous tissue and chronic inflammatory infiltrates in IPT compared with
the acute inflammatory infiltrates in an abscess.[9]
Treatment of IPT still remains a controversial point in the literature. In general,
IPTs have a benign clinical course. However, despite their benign nature, some authors
have reported their recurrence and potential for malignant transformation.[10] In the presence of favorable anatomic location and lack of contraindications to
surgery, some authors have recommended radical resection of these lesions. Others
opine that conservative approaches including antibiotics, nonsteroidal anti-inflammatory
drugs, steroids, and biliary drainage should be prioritized.[9] Hence, the most important step toward correct treatment is accurate diagnosis.
In conclusion, we present a case of hepatic IPT that can mimic both benign and malignant
entities. Our case demonstrates the diagnostic challenge of this entity, which has
nonspecific imaging findings. In our patient, the presence of a thick-walled multiloculated
cystic lesion with concomitant diverticulitis weighted the differential more toward
an abscess. Although rare, IPT should be considered in the diagnosis of focal hepatic
lesions in a patient with abdominal pain, fever, elevated liver enzymes, and with
nonspecific imaging features, especially in the setting of coexisting inflammatory
diseases in the abdomen. Histopathologic diagnosis in these cases would be prudent
to appropriate management and prevent patients from being subjected to unnecessary
surgical intervention.
