INVITED REVIEW

Inflammatory Myofibroblastic Tumor of

the Liver in Children

Sudhan Nagarajan, ySomasundaram Jayabose, zWhitney McBride, Indu Prasadh,

jj
Vijayakumar Tanjavur, Michael R. Marvin, and jjManuel I. Rodriguez-Davalos

ABSTRACT
Inflammatory pseudotumors, now more aptly termed inflammatory
myofibroblastic tumors (IMTs), are uncommon benign neoplasms, which
have been reported in most organs and tissues in the body. Originally
described and commonly found in the lung, they are also found in the liver
of children and adults. We review the literature and analyze the features
of the hepatic IMTs reported in children, along with a case report of a
15-month-old boy who had a persistent IMT in the liver and underwent
surgical resection for the same following a trial of conservative management.
Key Words: inflammatory myofibroblastic tumor, liver resections,
pediatric liver tumors

(JPGN 2013;57: 277280)

nflammatory myofibroblastic tumors (IMTs) are a group of

predominantly benign lesions, which are increasingly reported
in the literature. These lesions have a characteristic histological
picture comprising a spindle cell proliferation with a chronic
inflammatory infiltrate of plasma cells, lymphocytes, and histiocytes (1). These tumors can be found in various tissues and organs
in the body. Originally described in the lung, these lesions
have been occasionally reported in various extrapulmonary sites,
including the liver, skin, orbit, gingiva, breast, thyroid, thymus,
spleen, lymph nodes, and salivary glands (2). IMT has emerged
from the broader definition of inflammatory pseudotumor and
has distinctive clinicopathological features (3). Herein we report
a case of IMT of the liver and its management in a 15-month-old
boy, and review the literature on hepatic IMT in children.
A 15-month-old infant was noted to have an enlarged liver
(3 cm below the costal margin) on routine physical examination.
The patient was born at 32 weeks gestation with a birth
weight of 1.8 kg without any significant perinatal complications.
At 12 months of age, the patient had microcytic anemia with
Received October 24, 2012; accepted May 28, 2013.
From the
Department of Surgery, Drexel University College of Medicine,
Philadelphia, PA, the yDepartment of Pediatric Hematology and Oncology, the zDepartment of Pediatric Surgery, New York Medical College,
Valhalla, the Department of Pediatrics, Brookdale University Hospital,
Brooklyn, NY, the jjDepartment of SurgeryTransplant, Yale University, New Haven, CT, and the Division of Transplant Surgery, University of Louisville, Louisville, KY.
Address correspondence and reprint requests to Manuel RodriguezDavalos, MD, Department of SurgeryTransplant, FMB 121, 333
Cedar Street, Yale University School of Medicine, New Haven, CT
06510 (e-mail: manuel.rodriguez-davalos@yale.edu).
The authors report no conflicts of interest.
Copyright # 2013 by European Society for Pediatric Gastroenterology,
Hepatology, and Nutrition and North American Society for Pediatric
Gastroenterology, Hepatology, and Nutrition
DOI: 10.1097/MPG.0b013e31829e0b3b

JPGN

Volume 57, Number 3, September 2013

hemoglobin of 8.7 g/dL, mean corpuscular volume (MCV) of

67.3, and reticulocyte distribution width of 17.1, suggestive of iron
deficiency anemia, but did not respond to oral iron therapy. In fact,
the hemoglobin gradually decreased to 6.2 g/dL at 15 months of age,
when the enlarged liver was noted. The white blood cell count was
7700 cells per microliter with a normal differential and the platelet
count was increased (868,000 cells per microliter). The iron studies
were suggestive of chronic inflammation: serum iron 14 mg/dL,
total iron-binding capacity (TIBC) 252 mg/dL, transferrin
saturation 6%, and serum ferritin 140. The C-reactive protein
(CRP) was 11.9 mg/L and erythrocyte sedimentation rate (ESR)
was 70 mm/hour. Serum a-fetoprotein (AFP), liver function tests,
and coagulation tests were normal. An abdominal sonogram
showed a 4.6 cm  4.6 cm  5.0 cm mass in the left lobe of the
liver with central calcification. Contrast-enhanced computerized
tomography (CT) scan of the liver revealed a mass in the left lobe
of the liver with coarse central calcifications (Fig. 1), similar to
the sonogram. There was enhancement of the mass on the portal
venous phase and there was no evidence of any mass or adenopathy
in the thorax or pelvis. The left portal vein was displaced but
patent. The other portal vein and hepatic vein branches were patent.
A CT-guided needle biopsy of the mass was done at the time of
diagnosis (Fig. 2).
In view of the normal AFP level, the radiologic findings were
considered to be suggestive of a mesenchymal hamartoma. Because
there is a considerable debate in literature that such hamartomas
may resolve spontaneously, and in view of the general condition,
the patient was simply observed for the next 8 months with regular
ultrasound examinations, and follow-up of complete blood cell
(CBC) count, ESR, CRP, and AFP. During this time, the tumor
did not increase in size, and the ESR and CRP remained elevated:
78 to 91 mm and 6.4 to 7.7, respectively, and the anemia and
microcytosis persisted, with hemoglobin levels of 9.3 to 9.8 g/dL
and MCV values near 65. These laboratory findings were suggestive of a diagnosis of IMT. Eight months after the initial diagnosis
of the hepatic mass, the patient underwent complete surgical
resection of the mass. The histopathology confirmed the diagnosis
of IMT (Figs. 35).
A month after surgery, ESR was 6 mm, CRP was
0.2, hemoglobin was 11.5, MCV 76, serum iron 21, and TIBC
318. Eight months later, ESR was 1, CRP <0.1, and serum iron
was 92. At the last follow-up visit, 12 months after surgery, the child
was doing well, and the sonogram revealed no mass in the liver.

DISCUSSION
IMTs have been referred to in the existing literature by
various synonyms such as inflammatory pseudotumor, plasma cell
granuloma, pseudosarcomatous myofibroblastic proliferation,
xanthomatous pseudotumor, and inflammatory myofibrohistiocytic
proliferation (4). Coffin et al (5) emphasized the term

277

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Nagarajan et al

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Volume 57, Number 3, September 2013

FIGURE 1. Contrast-enhanced computed tomography showing

enhancing mass in the left lobe of the liver with coarse calcifications.

FIGURE 3. Hematoxylin and eosin stain showing collagenous areas

and inflammatory component of tumor with entrapped bile ducts.
Original magnification 40.

inflammatory myofibroblastic tumor to describe these lesions

more precisely and they also found that these tumors are
associated with anemia, fever, thrombocytosis, and hypergammaglobulinemia. Although IMT has been considered to have
emerged from the broader category of inflammatory pseudotumor,
the usage of both these terms interchangeably in the past has
made the analysis of these lesions difficult. We reviewed the
case reports of hepatic IMT children in an attempt to evaluate
their characteristics as a whole. The main features are depicted in
Table 1 (4,814,1936).
We found that 35 patients (16 males and 17 females; sex not
indicated in 2 patients), including our patient, reported in the
scientific literature from 1971 to 2008 searched through the
electronic databases PubMed and HighWire. The key words
inflammatory pseudotumor, IMT, pediatric, hepatic, and liver were
used to retrieve the relevant articles. The patients ages ranged from
3 months to 15 years. Symptoms were both constitutional and local.
Fever was present in 14 patients (40%), whereas other constitutional
symptoms such as anorexia, weight loss, and night sweats were
seen in <20%. The predominant gastrointestinal symptoms were
abdominal pain in 15 patients (43%), abdominal mass in 10 patients
(28%), and vomiting and diarrhea in 5 patients (14%) each.
Jaundice present in 8 patients (23%) was either caused by the
presence of tumor in the porta hepatis or involvement of the hilum.

The etiology was considered to be idiopathic in the majority of

patients and infective or immunosuppressive in the remaining
few who had preexisting or associated illnesses; however, the exact
etiopathogenesis was not established in any of the cases.
The size of the tumors ranged from 2 to 14 cm. In >90% of
patients, the tumors were single lesions. Hilar infiltration was
present in one-third of the cases. Involvement of both lobes was
rare, and was reported in only 1 patient. Inflammatory markers
(elevated white blood cell count, ESR, and CRP) were elevated
either singly or in combination in almost half of the patients.
Liver function tests indicated obstruction in patients with hilar
involvement. AFP level was normal in all patients.
Ultrasonography has been used in most of the patients and
these lesions are isoechoic or hypoechoic; however, they present
as a mosaic pattern in some patients. CT scan with contrast
shows IMT as an ill-encapsulated but well-demarcated mass with
peripheral enhancement in most cases and homogenous enhancement in some (6). Magnetic resonance imaging shows low signal
intensity mass on both T1- and T2-weighted images; however, it has
not been definitively diagnostic for these lesions (7). Angiographic
findings are not specific (8,9). Needle biopsies done with ultrasound guidance reveal a polymorphous infiltrate chiefly made up
of lymphocytes and plasma cells associated with a fibrous stroma
with fibroblasts, myofibroblasts, and macrophages (10).

FIGURE 2. Computed tomographyguided needle biopsy of mass;

hematoxylin and eosin stain at original magnification 40.

FIGURE 4. Hematoxylin and eosin stain showing cellular components

of the tumor, plasma cellslymphocytes. Original magnification 40.

278

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JPGN

Volume 57, Number 3, September 2013

Inflammatory Myofibroblastic Tumor of the Liver in Children

FIGURE 5. Cytokeratin AE 1 to 3 immunostaining of the tumor

showing entrapped bile ducts (brown); original magnification 40.

The natural history of IMTs is unpredictable (10). It can

be locally invasive and can infiltrate into adjacent structures.
At the other end of the spectrum, it can regress spontaneously
without treatment (11). Complete resolution of IMT with conservative management with antibiotics or nonsteroidal antiinflammatory drugs has been described in 2 reports, which recommend a period of watchful waiting for these benign lesions (12,13).
Surgical removal of tumors was done in 30 (85%) patients,
but the type of surgical resection was variable. Surgical options
include wide excision, segmentectomy, and lobectomy. Trisegmentectomy and liver transplantation are done when significant
involvement of the porta hepatis precludes less extensive resection.
Complete resection results in cure and no recurrences have been
reported in any of the patients on follow-up (minimum of 6 months).
Liu et al (14) observed IMT in post-Kasai procedure patients
and they underwent removal of the tumors during living donor
liver transplantation.

TABLE 1. Treatment methods and outcomes of IMFT in the published literature

Treatment method
Conservative

Segmentectomies and
wedge resections

Major resections
and lobectomies

Liver transplantation

Prednisone
Antibiotics
NSAIDs
Observation
Segmentectomy
Segmentectomy
Segmentectomy
Partial segmental resection
Partial left lobectomy
Left lateral segmentectomy
Wedge resection
Wedge resection
Wide excision
Wide excision
Wide excision
Right lobectomy
Left lobectomy
Left hemihepatectomy
Right lobectomy
Right lobectomy
Left lobectomy
Left lobectomy splenectomy
esophagogastrectomy
Right lobectomy
Left lobectomy
Extended right hepatectomy
Extended left hepatectomy
hepatic artery and portal
vein reconstruction
Right lobectomy
Biopsy, total hepatectomy,
transplantation
Ex vivo left trisegmentectomy
liver transplant
Trisectionectomy and then
transplantation
LDLT
LDLT
LDLT

Author/year

Age

No. of lesions/site

Outcomes

Hertzer et al (19)/1971
Lykavieris et al (12)/2000
Koea et al (36)/2003
Dasgupta et al (11)/2004
Griseri et al (26)/1992

1y
4y
2y
3y
12 y

S
S
Multiple
S
S

PH
LL
Both lobes
RL
LL

Portal hypertension
Recovery
Recovery
Recovery
Recovery

Bankole-Sanni et al (9)/1997
Karnak et al (4)/2001
Sakai et al (7)/2001
Loke et al (29) 1994
Current patient/2007
Anthony et al (24)/1986
Newbould et al (27)/1992
Passalides et al (30)/1996
Vanthournout et al (10)/1998
Lacaille et al (32) /1999
Someren et al (20)/1978

9y
6y
2y
2y
1y
12 y
2y
14 y
4y
9 mo
4.5 y

S
S
S
S
S
S
S
S
S
S
S

RL
LL
RL
LL
LL
RL
LL
RL
RL
LL
RL

Recovery
Recovery
Recovery
Recovery
Recovery
Recovery
Recovery
Recovery
Recovery
Recovery
Recovery

Daimaru et al (21)/1983
Kaneko et al (23)/1984
Anthony et al (24)/1986
Hata et al (25)/1992
Hata et al (25)/1992
Vujanic et al (8)/1992

9 mo
10 y
10 y
7y
6y
15 y

S
S
S
S
S
S

LL
LL
RL
RL
LL
LL

Recovery
Recovery
Recovery
Recovery
Recovery
Recovery

Broughan et al (28)/1993
Hsiao et al (33)/1999
Kaneko et al (34) 2001
Ueda etal (13)/2003

13 y
5y
6y
7y

S
S
S
S

RL
LL
RL
LL

Recovery
Recovery
Recovery
Recovery

Fangusaro et al (35)/2003
Heneghan et al (22)/1984

8y
8y

S
Multiple

RL
RL

Recovery
Recovery

Kim et al (31)/1996

5y

LL

Recovery

Dasgupta et al (11)/2004

7y

PH

Recovery

Liu et al (14)/2007
Liu et al (14)/2007
Liu et al (14)/2007

2y
10 y
3y

S
S
Multiple

Recovery
Recovery
Recovery

LDLT living donor liver transplantation; LL left lobe; NSAIDs nonsteroidal anti-inflammatory drugs; PH porta hepatis; RL right lobe;
S single.

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Nagarajan et al

JPGN

We undertook surgical resection in our patient because the

tumor and the associated inflammatory state failed to resolve even
after 8 months of conservative management.
Anaplastic lymphoma kinase gene rearrangements have
been noticed in 50% of patients with IMT (15). Chun et al (16)
have found in a limited series that anaplastic lymphoma kinase
expression was associated with localized disease at presentation and
an improved prognosis. Also, it has been reported that aneuploidy
increases the incidence of local recurrences (17). A neoplastic
variant, inflammatory fibrosarcoma, characteristically presents
with aggressive behavior and multiple recurrences (18).

CONCLUSIONS
IMTs of liver are rare, benign tumors occurring in all age
groups. Clinical features include asymptomatic mass, abdominal
pain, vomiting, fever, and signs and symptoms of chronic inflammation, including microcytic anemia and elevated CRP. Imaging
studies are not characteristic and IMTs are usually confused with
other neoplasms. Serum AFP is normal in all cases. Imaging-guided
needle biopsies enable a diagnosis in doubtful cases, although the
sensitivity and specificity of this modality remain to be established.
Surgical resection is indicated if the lesion persists or progresses
after a trial of conservative therapy, or manifests evidence of local
infiltration into vital structures, or of malignant transformation.
Complete resection is curative in most patients.

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