Inflammatory myofibroblastic tumor of the liver: A case report and review of literature

Table 1 Case reports

Ref.	n	Age (yr)	Gender	Clinical and laboratory findings	Radiology	Localization	Tentative diagnose	Treatment	Histology	Follow up
Watanabe et al[32], 2019	1	70	Female	Incidental finding	CT unenhanced, low density	Right lobe	HCC	Right partial hepatectomy	Unencapsuled, partly ill defined expansive mass, myofibroblast-, fibroblast cells, inflammatory cells, SMA+, cytokeratins AE1/AE3+; CK7,CK18+, Desmin-, CD68-, IgG4-, ALK-	No recurrence after 7 mo
Al-Hussaini et al[24], 2019	1	8	Male	FUO, weight loss, hepatomegaly, normal liver enzymes, CRP↑	MRI: Contrast-enhancing, hyper-intense, well-defined lesion	Right lobe	Infection DD malignancy	Right lobe hepatectomy	Multinucleated giant cells, inflammatory cells, SMA-, ALK-1-, CD-21- CD-23- CD-68+	No recurrence after 4 mo
Lu et al[33], 2018	1	20	Male	FUO, jaundice, abdominal pain, CA 19-9↑	MRI: Multiple lesions, intrahepatic bile duct was significantly dilated	Left lobe	CCC	Biopsy, patient declined operation, PTCD	Spindle cells proliferation and infiltration by mixed inflammatory cells, ALK+, SMA+	NM
Jin et al[5], 2017	1	42	Female	Fatigue, fever, pale conjunctivae; Hb↓, Lc↑	U/S: Hypoechoic mass with unclear border; CT: Low density lesion with mild enhancement	Right lobe	Liver abscess	Right posterior segmentectomy	Chronic inflammatory cells, spindle cells; CD68+, smooth muscle actin, ALK-	No recurrence after 32 mo
Mulki et al[22], 2015	1	50	Male	Abdominal pain, anorexia, mild fever, hepatomegaly	U/S: 2 hypodense masses, CT: + hepatic vein thrombus	Right lobe	Abscess with septic thrombus	Initial treatment: Biopsy, pigtail, antibiotics, secondary operation	Plasma cells, inflammatory cells, ALK, IgG4+	No residual disease
Obana et al[25], 2015	1	69	Male	FUO, CA 19-9 48 ng/mL (n: < 37 ng/mL), Diabetes mellitus II, Dyslipidemia, hypertension	U/S: Irregularly shaped, low-echoic mass; CT: Peripherally enhanced, MRI: T1W, central portion hyperintense	Right lobe Seg VI	CCC/HCC	Partial hepatectomy	Whitish-yellow mass 2 cm in size , inflammatory cell infiltrates, cholesterol cleft granuloma with focal abscess were observed in the central compartment , IgG4 -	NM
Guerrero Puente et al[26], 2015	1	75	Male	Weight loss, fever, intermittent night sweat, abdominal pain, CRP↑, leukocytosis, cholestasis hypertension, hypercholesterinemia	CT: 8 cm heterogeneous focal lesion, portal branch thrombosis, lymphadenopathy; MRI: T2W isointense, T1W discretely hypointense, cystic–necrotic areas, perilesional edema	Left lobe	Inflammatory disease	CT-guided biopsy followed by antibiotic therapy	Inflammatory pseudotumour, vimentin+, AML+, desmin−, CD68−, ALK−, with no light chain restriction and a low proliferative index (15%)	Partial remission after 1 mo, almost complete remission after 6 mo
Onieva-González et al[27], 2015	1	70	Male	Low-grade fever, asthenia, weight loss and oligoarthritis, lung tuberculosis, diabetes, gouty arthritis, renal lithiasis and colon diverticulitis	CT: Thickened gallbladder wall, poorly-defined hypodense lesion of 17 mm in the gallbladder bed, U/S: Nodule; MRI: Hypointense in T2 sequences; PET: No metabolism	Seg. V	Liver abscess	Antibiotic therapy, after 4 mo later fine needle biopsy followed by laparoscopic biopsy and cholecystectomy with the lesion in the gallbladder bed	Lymphoid infiltration without malignancy signs, compatible with an inflammatory pseudotumour	NM
Chang et al[50], 2014	1	38	Male	Fatigue, abdominal distension and weight loss, jaundice, hepatomegaly, bilateral ankle edema	U/S: Complex mass; CT: Large cystic or necrotic mass; MRI: T2W: Cystic portion hyperintense to liver parenchyma, surrounded by a hypointense rim. T2W: Hyperintense compared to liver parenchyma	Bilateral	N/A	Ultrasound-guided and open biopsy, followed by resection	Cellular spindle-cell proliferation with heavy inflammatory infiltrate consisting primarily of plasma cells and lymphocytes	Recurrence
You et al[35], 2014	1	43	Male	Chronic cough, right-upper-quadrant pain, anorexia for 3 mo, leukozytosis, elevated platelet count	U/S: 18 cm mass with slightly echogenic center; MRI: Large mass with central dark area and some peripheral spokes; CT: Mass, 20 cm × 17 cm × 18 cm, with extensions into the medial segment of the left hepatic lobe, hypervascular nodular area with enhanced density at the periphery and hypoattenuating density centrally	Right lobe	Fibrolamellar hepatocellular carcinoma or CCC	Percutaneous needle core biopsy > NM	Bland spindle cell proliferation amidst small mature lymphocytes, numerous plasma cells, histiocytes, and few neutrophils. Spindle cells showed a storiform pattern with large areas of necrosis; cytokeratin (CAM 5.2) -, cytokeratin 5/6 -, actin-, CD34-, CD117-, DOG-1-, desmin-, CD68-, S100-, Pan-melanoma-. Spindle cells were negative for CD21, CD23, CD35, ALK-1. Epstein-Barr virus-encoded small RNA in situ hybridization (EBER) showed large numbers of Epstein-Barr virus positive cells, including some spindle cells	NM
Durmus et al[36], 2014	1	67	Female	Moderate diffuse abdominal tenderness, focus over epigastrium	U/S: Heterogeneous hypoechogenic tumor; CT: Contrast enhancing mass with irregular confluent non-enhancing areas in the center with a hypodense late enhancing rim and no wash-out in the late phase, MRI: In T1W hypointense borders, well defined without fatty components. T2W showed a heterogeneous slightly hyperintense lesion with an ill-defined hyperintense rim	Segment IV	Malignancy	Left hemihepatectomy with partial excision of the adherent abdominal wall and diaphragm	Tumor with fibrosis and partially necrotic tissue infiltrated by inflammatory cells, predominantly plasma cells, and also pigmented macrophages and granulocytes	NM
Wong et al[37], 2013	1	56	Female	Right-upper-quadrant abdominal pain, renal transplant	U/S: 2 cm × 2.4 cm mass in the left hepatic lobe with associated biliary duct dilatation, MRI: atrophic left liver lobe with multiple strictures and distal duct dilatation. 2-cm lesion at the origin of the left hepatic duct	Left lobe	Primary hepatic tumor	Surgical resection	Dense hyalinised stroma and scattered, histiocytic and lymphocytic inflammation	NM
Kruth et al[38], 2012	1	NM	NM	FUO CRP↑	Gastroscopy, CT lung and abdomen, MRI: 3.3 cm lesion	Seg. VI	Adenoma, focal nodular hyperplasia or HCC	Surgical resection	NM	No recurrence after 1 yr
Chablé-Montero et al[39], 2012	1	23	Female	Fever, diaphoresis, right-upper-quadrant abdominal pain	U/S and CT: Heterogenous rounded hepatic lesion of 7 cm in greatest dimension	Right lobe	Pyogenic hepatic abscess	Antibiotics, later right hepatic lobectomy	Grossly a non-encapsulated but well demarcated hepatic tumor with central necrosis of 11 cm in greatest dimension; microscopically: Spindle myofibroblastic cells arranged in fascicles. Leukocytes, lymphocytes, plasma cells, SMA+	NM
Kayashima et al[30], 2011	1	57	Female	Asymptomaticlaparoscopic calculous cholecystectomy 3 yr ago	U/S: 3 liver masses, CT: 1 intra- and 2 extrahepatic lesions; MRI: three high‐intensity lesions; PET: Abnormal accumulation in all lesions	Right lobe	CCC	Surgical resection (tiny black‐colored nodules within the abdominal cavity and spilled gallstones)	Inflammatory granuloma located at liver parenchyma	No recurrence after 6 mo
Huang et al[40], 2012	1	30	Male	Right upper abdominal pain; CEA↑; 2 yr after renal transplant	CT: Low-density mass, about 30 mm in diameter, well defined, and with peripheral enhancement	Caudate lobe	HCC or liver abscess	Hepatic caudate lobectomy with complete resection of the mass	Mixture of spindle-shaped myofibroblastic cells and chronic inflammatory cells; SMA+	NM
Beauchamp et al[41], 2011	1	74	Female	FUO	CT: Numerous hypodense lesions scattered throughout the liver	NM	NM	Liver biopsy	IMT	NM
Al-Jabri et al[29], 2010	1	69	Male	Right upper quadrant pain, nausea, vomiting, recent weight loss, rheumatoid arthritis and bronchiectasis, CRP↑, cholestasis (normal Bili)	U/S: Ill-defined area, CT: multiple low attenuation lesions	Right lobe	Cholecystitis, malignancy	Fine needle biopsy	Presence of benign hepatocytes, acellular debris and a mixture of acute and chronic inflammatory cells	No recurrence after 3 mo
Salakos et al[43], 2010	1	10	Male	Fever, weight loss, fatigue, tachycardia, hepatomegaly, leukocytosis, platelet count ↑	U/S: Space occupying lesion in the liver; CT: Large lesion with sold and cystic parts and heterogenous enhancement	Right and left lobe	NM	Biopsy followed by conservative treatment (ceftriaxone, clindamycin, NSAR)	Hyperplastic cholangioles, myofibroblasts and fibroblasts, infiltrate of lymphocytes, eosinophils and neutrophils; ALK+	Partial response after 2 mo, complete response
Ueda et al[45], 2009	1	79	Male	Leukocytosis	U/S: Hypoechoic lesion, 3 cm in diameter, with several stones. CT: Low density area in segment V; MRI: Lesion of slightly low signal intensity; MRCP: Lesion of moderate-to-high signal intensity on T2W	Right lobe	Inflammation due to cholangitis with intrahepatic bile duct stones	1. ERCP: Sphincterotomy, antibiotics because of common bile duct stone; 2. Relapse of symptoms 4 wk later > resection	Grossly gray, fibrotic, solid tumor, intrahepatic bile duct stones. Proliferation of diffuse myofibroblastic and mesenchymal cells in a mixed myxoedematous, dense fibrotic stroma, with many small vessels and marked infiltration by various acute and chronic inflammatory cells	No recurrence after 18 mo
Sürer et al[7], 2009	1	48	Female	Weakness, fever, weight loss, right upper abdominal pain, Lc-, neutrophil 75.3%, liver function normal	U/S: Single hypoechoic lesion in right lobe	Right lobe	NM	Resection	No capsule, light brown, no necrosis, spindle cells, granulation-tissue type vessels, chronic inflammatory cells on loose, edemateous, myxoid stroma, CD 38+, SMA+, ALK+, desmin, EMA-	2 yr no recurrence after 2 yr
Manolaki et al[47], 2009	1	9	Female	Fever, mild anorexia, intermittent epigastric pain	U/S: Hypoechoic lesion, lymph node at porta hepatis, CT: hypodense space-occupying lesion	Left lobe	NM	Biopsy, secondary left lateral segmentectomy with lymph node excision	Pale and firm lesion (3.5 cm × 2.5 cm × 3.0 cm) with whitish solid infiltrations extending to the capsule of the liver. Proliferation of spindle-shaped cells arranged in short fascicles with an ill-defined mark. Inflammatory cells, predominantly lymphocytes, plasma cells and eosinophils; vimentin+, SMA+, CD68+,TBC+	No recurrence after 3 yr

CT: Computed tomography; MRI: Magnetic resonance imaging; FUO: Fever unknown origin; CRP: C-reactive protein; CCC: Cholangiocarcinoma; HCC: Hepatocellular carcinoma; PTCD: Percutaneous transhepatic cholangio drainage; NM: Not mentioned; U/S: Ultrasonography; Hb: Haemoglobin; LC: Leukocytes; TC: Thrombocytes; T1W: T1-Weighted; T2W: T2-Weighted; Chron Hep B: Chronic Hepatitis B; Seg: Segment; ↑: Increase; ↓: Decrease; WBC : Wight blood cells; SMA: Smooth muscle actin; ERCP: Endoscopic retrograde cholangiopancreatography.

Table 2 Clinical studies of > 2 patients

Ref.	n	Age (yr)	Gender	Clinical and laboratory findings	Radiology	Localization	Tentative diagnose	Treatment	Histology	Follow up
Park et al [28], 2014	45	65 (29-84)	Male/female (26/19)	Abdominal pain (n = 16) fever (n = 11), malaise (n = 5) weight loss (n = 4); CRP↑ (n = 31), leukocytosis (n = 10), CEA (n = 1) CA 19-9 (n = 1); hypertension, tuberculosis, chronic Hepatitis B	CT scan: Hypo-attenuating lesions in 40 patients, MRI: Low signal intensity lesion at T1W image in 86.4% and relatively homogenous high signal intensity lesion at T2W image in 76.2%	Right lobe (n = 27), left lobe (n = 14), both (n = 4)	Malignancy (n = 26, 57.8%), abscess (n = 11, 24.4%)	Percutaneous needle biopsy (n = 35), surgical resection (n = 9), both (n = 1)	Chronic infiltration of various inflammatory cells (plasma cells, lymphocytes, neutrophils, and eosinophils) and fibrous stroma	No recurrence after median follow-up of 8 mo
Ahn et al [42], 2011	22	34- 76	Male/ female (16/6)	Abdominal pain (n = 12), febrile (n = 5), malaise (n = 1), asymptomatic (n = 4), leucocytosis (n = 6), hyperbilirubinaemia (n = 3), alkaline phosphatase↑ (n = 10), liver enzymes ↑ (n = 5), CA 19-9 ↑ (n = 5), AFP↑ (n = 1) ; associated biliary disease (n = 15), malignancy (n = 4)	Solitary (n = 17); multiple (n = 5), median size 3 cm (1.1-9.6 cm), non-enhanced CT: Hypoattenuating lesions (n = 22), enhanced CT: Central hypoattenuating areas and a delayed hyperattenuating periphery (n = 18), multiseptate appearance with hyperattenuating internal septa and periphery (n = 3), hypoattenuation up to the equilibrium phase (n = 1)	Right lobe n = 10, left lobe n = 9, both n = 3, (mostly seg. IV n = 12)	IPT (n = 12), malignancy (n = 4), recurrence of malignancy (n = 2), abscess (n = 4)	Percutaneous needle biopsy (n = 18), incisional biopsy (n = 1) --> surgical resection (n = 3); liver resection (n = 3) without prior biopsy, 16 patients conservatively, 6 patients with surgical resection	Histiocytic cell infiltration with negative IgG4 (n = 17), lymphoplasmacytic type (n = 5) with positive IgG4 (n = 4)	Post conservative treatment: 10 complete remission after 15 mo; 5 partial remission after 4 mo, post resection: Mortality n = 2 (myocardial infarction, peritoneal seeding)
Geramizadeh et al [44], 2009	2	14	Male	Chills, fever, anorexia > 8 kg weight, leukocytosis	CT: Well-defined heterogeneous mass with central areas of necrosis and a slightly hyperdense rim	Left lobe	Abscess	Resection	Creamy grey mass with a vague whorling appearance. Plasma cells with varying degrees of fibroblastic proliferation admixed with lymphocytes, eosinophils and macrophages	No recurrence after 1 yr
		15	Male	Hepatitis B positive, weight loss	Well defined liver mass	NM	Malignancy	Fine needle biopsy	6 cm liver mass, fibroblastic proliferation, many plasma cells and eosinophils	No recurrence after 2 yr
Yamaguchi et al [17], 2007	3	52	Male	Epigastric pain, appetite loss, weight loss, fever	U/S and CT: Hepatic mass in left lobe	Left lobe	IPT	Follow up	NM	Complete remission after 1 yr
		58	Male	Auxiliary finding	CT: Low density mass in the right lobe enhanced during the delayed phase	Right lobe	CCC	Biopsy > no treatment, follow up	IMTL	NM
		57	Female	Sigmoid cancer planned for resection	MRI: 2 metastases with low-intensity signal on T1, a slightly high-intensity signal on T2	Right lobe	Hepatic metastasis	Intraoperative right portal vein embolization	NM	NM
Milias et al[46], 2009	4	35	Male	Abdominal and bone pain, fatigue, malaise, hematuria, WBC↑	CT: Liver abscess right upper abdominal quadrant	Right lobe	Liver abscess	Drainage followed by right hepatectomy	Many plasma cells, densely collagenous bundles between a plasma cell-rich infiltrate	NM
		56	Male	Right upper abdominal pain, malaise	CT: Liver abscess	Right lobe	Liver abscess	Drainage followed by right hepatectomy	Inflammatory response to hepatic abscess
		75	Female	Moderate upper quadrant pain, nausea, and vomiting	U/S: Cystic lesion, CT: Cystic lesion, slight dilatation of intrahepatic bile ducts	IVB	Cholangitis/ Cystadenoma	Biopsy followed by Seg. IVB resection	Central granulation, fibrosis and chronic lymphoplasmacytic infiltrate, no features of neoplasia. Inflammatory pseudotumor
		47	Female	Right upper quadrant pain, jaundice, fever, pruritus	CT: Marked dilatation of the intrahepatic biliary tree	Right lobe	CCC	Seg. III resection, secondary right hepatectomy	Widespread chronic inflammatory infiltrate with lymphocytes and plasma cells, numerous lipid-laden macrophages, no malignancy

CT: Computed tomography; MRI: Magnetic resonance imaging; FUO: Fever unknown origin; CRP: C-reactive protein; CCC: Cholangiocarcinoma; HCC: Hepatocellular carcinoma; PTCD: Percutaneous transhepatic cholangio drainage; NM: Not mentioned; U/S: Ultrasonography; Hb: Haemoglobin; LC: Leukocytes; TC: Thrombocytes; T1W: T1-Weighted; T2W: T2-Weighted; Chron Hep B: Chronic Hepatitis B; Seg: Segment; ↑: Increase; ↓: Decrease; WBC: Wight blood cell.