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Clinicopathological features and post-resection outcomes of inflammatory pseudotumor of the liver

Backgrounds/Aims Hepatic inflammatory pseudotumor (HIPT) is a rare disease characterized by chronic infiltration of inflammatory cells and area of fibrosis. The objective of this retrospective observational study was to investigate clinicopathological features and outcomes of patients who underwent hepatic resection (HR) for HIPT. Methods From 2009 to 2018, seven patients with HIPT underwent HR, accounting for 0.06% of 11,979 adults who underwent HR at our center. Results These seven patients included five men and two women. Their mean age was 62.3±11.6 years. In four patients with hepatitis B virus (HBV)-associated liver cirrhosis or chronic hepatitis, liver masses were suspected of hepatocellular carcinoma (HCC) or combined HCC-cholangiocarcinoma based on imaging studies. In three patients without HBV infection, two patients were suspected of HCC, for whom liver biopsy was not performed. One patient was suspected of liver abscess or HIPT, for whom percutaneous liver biopsy was performed and the mass was diagnosed with HIPT. However, this patient underwent HR owing to abdominal pain. No patient presented with abnormally elevated levels of alpha-fetoprotein, protein induced by vitamin K absence or antagonist-II, or CA19-9. During a mean follow-up period of 76.4±34.8 months, no patient experienced recurrence of HIPT. Conclusions HIPT, a rare form of liver disease, is often misdiagnosed as malignant liver tumor. Active histological diagnosis is warranted for patients with suspected HIPT to avoid unnecessary operation. HR can be indicated in case of diagnostic ambiguity of HIPT or under a clinical diagnosis of malignant liver tumor.


INTRODUCTION
Inflammatory pseudotumor (IPT) is a rare disease characterized by chronic infiltration of inflammatory cells and area of fibrosis. 1 It is also known as inflammatory myofibroblastic tumor or plasma cell granuloma. 2 Its etiology is uncertain, although infectious condition, autoimmune phenomenon, and systemic inflammatory response syndrome have been suggested to play roles in its pathogenesis. [2][3][4][5] Recently, IPTs are more frequently recognized than before probably due to frequent abdominal imaging studies.
Despite recent development of radiologic imaging studies, it is still difficult to differentiate hepatic inflammatory pseudotumor (HIPT) from malignant tumors (such as hepatocellular carcinoma [HCC], intrahepatic cholangiocarci-noma [ICC], and metastatic cancer 6,7 ) and liver abscess showing incomplete liquefaction and granulation. 8,9 Treatment for HIPT has not been established yet. [9][10][11][12] Due to its diagnostic ambiguity, some patients undergo surgical resection and other patients are managed with antibiotics, nonsteroidal anti-inflammatory drugs, or no medication. 2,7,9,[13][14][15] The objective of this study was to investigate clinicopathological features and outcomes of patients who underwent hepatic resection (HR) for HIPT.

Patient selection
Liver resection database at our institution was extensively searched to identify patients diagnosed with HIPT. Preoperative evaluation, surgical procedures, and postoperative follow-up Routine preoperative evaluation was performed for primary liver tumors as described previously. 16 In general, patients who underwent HR for benign diseases were followed up every 6 months during 3 years after surgery and every 1-2 years thereafter as part of routine health screening.

Statistical analysis
Numerical data are presented as means and standard deviations. All statistical analyses were performed using SPSS version 22 (IBM, New York, NY, USA).

Patient demographics and preoperative diagnosis
Clinicopathological features of seven patients with HIPT are described in Table 1 In this study reflecting the reality, the majority of liver masses were clinically diagnosed with HCC. Thus, percutaneous liver biopsy was performed in only 2 of 7 patients.
The etiology of HIPT is unknown yet, although inflammatory pattern of pathology and its associated laboratory findings have been suggested to have possible association with underlying infection via hepatobiliary tract in several studies. 2,5 Some studies have shown that 68%-80% of patients have hepatobiliary tract disease. 14,17-20 Abdominal pain, fever, and elevated inflammatory markers (including erythrocyte sedimentation rate, C-reactive protein, and leukocyte count) are common in HIPT cases. 2,9,14,17,18 These findings suggest the association of an underlying infectious condition with HIPT.
HIPT presents as a large solitary mass. It occurs predominantly in the right lobe, although multicentricity has been also described. 2,17,21-23 A Korean multicenter has also shown that the mean size of mass is 4.4 cm and that the majority of patients have a single tumor with right liver predominance. 9 Results of the present study showed that a solitary mass of variable size without locational predominance was the common finding.
In the literature, HIPT has shown inconsistent appearance on radiologic studies without specific image findings. 2,8,9,17  Because of such ambiguity in imaging diagnosis, histological diagnosis is essential to diagnose HIPT accurately.
It is known that the clinical course and prognosis of HIPT are favorable with conservative treatment. 2,5,8,9,14,17,23 In the present study, no recurrence occurred during a mean This study has several limitations, including its retrospective design and inclusion of a small number of patients treated at a single center. Multi-center studies are needed in the future to evaluate characteristics of this very rare disease.
In conclusion, HIPT is a rare form of liver disease that is often misdiagnosed as malignant liver tumor. Active histological diagnosis is warranted for patients with suspected HIPT to avoid unnecessary operation. HR can be indicated in case of diagnostic ambiguity of HIPT or under a clinical diagnosis of malignant liver tumor.