Inflammatory Pseudotumor of the Liver

Rosa and colleagues present a case of a hepatic inflammatory pseudotumor that was correctly diagnosed via fine-needle biopsy and that spontaneously resolved without treatment.¹ The patient was a white Portuguese man who had no significant medical history and had never traveled outside of Europe. He presented with a 4-week history of intermittent fever, malaise, and abdominal discomfort. A thorough examination revealed a heterogeneous, solid, right hepatic lobe mass that was determined via biopsy to be an inflammatory pseudotumor. This well-documented case raises a number of important points.

Given the lack of uniform criteria for diagnosing inflammatory pseudotumors, it is difficult to obtain clear data from the literature regarding the incidence, anatomic distribution, natural history, and malignant potential of these lesions.^1–3 Not surprisingly, this difficulty has an impact on the understanding of the natural history of this condition as well as its prognosis and treatment.

The term “inflammatory pseudotumor” describes a heterogeneous group of mass-forming lesions that can involve many organs and that are characterized by a prominent inflammatory infiltrate as the predominant cellular component. There has long been confusion over the nature of these lesions, particularly since the term “inflammatory pseudotumor” has been synonymous with “inflammatory myofibroblastic tumor” in the literature when referring to pediatric soft tissue tumors.

Several lesions previously considered to be variants of inflammatory pseudotumors have recently been identified as different entities. The neoplastic variants of inflammatory pseudotumors include inflammatory myofibroblastic tumors associated with anaplastic lymphoma kinase (ALK-1) translocation, as well as inflammatory pseudo-tumor—like follicular dendritic cell tumors of the liver and spleen that are related to clonal Epstein-Barr virus infec-tion.^4,5 Some of these lesions represent true neoplasms. In addition, mycobacterial spindle-cell inflammatory pseudotumors of lymph nodes and tumefactive lesions associated with immunoglobulin (Ig) G4 are examples of infectious and autoimmune-induced inflammatory pseudotumors, respectively.^6–8 The etiology and pathogenesis of inflammatory pseudotumors remain unclear for a variety of tumorous inflammatory lesions that lack the features of the entities listed above (inflammatory pseudotumors, not otherwise specified).

An inflammatory pseudotumor of the liver is an uncommon, benign, tumor-like lesion that sometimes mimics a malignant tumor, particularly metastatic disease or cholangiocarcinoma.⁹ In the majority of cases, including the case presented by Rosa and associates, these inflammatory pseudotumors are most likely inflammatory or infectious in origin.¹ The lesions often appear to develop from a healing abscess or an inflammatory condition resulting from rupture of the bile duct and extravasation of bile into the tissue, which provokes a xanthogranulomatous inflammatory response that heals with scarring.

In our experience, most cases that have been thought to be inflammatory myofibroblastic tumors in the liver are better classified as inflammatory pseudotumors and represent a resolving inflammatory process. All 145 cases in a study we conducted at the Armed Forces Institute of Pathology had features of inflammatory pseudotumors rather than inflammatory myofibroblastic tumors.¹⁰ It is well recognized that inflammatory pseudotumors have a wide variability in histologic features that may be reflected in different areas of the same lesion. Therefore, adequate sampling in multiple sections is essential for establishing an accurate diagnosis. Our study identified 5 main histo-logic subgroups: a plasma cell—rich subgroup with aggregates of or diffuse lymphocytes, a mixed inflammatory cell subgroup, a granulomatous subgroup, a granulomatous subgroup with eosinophils, and a predominantly purulent subgroup.¹⁰ None of the cases in our study stained positive for infectious organisms, and immunostaining found no evidence of lymphomas, Langerhans cell histiocyto-sis, IgG4-related sclerosing disease, or ALK-1—positive inflammatory myofibroblastic tumors, unlike reported cases of inflammatory pseudotumors in the lungs.¹¹ Follow-up data revealed no patients with subsequent neoplasms, recurrences, or metastases.

Since inflammatory pseudotumors are so rare, they are usually surprising when found in a biopsy or resection specimen. However, astute clinicians should consider this diagnosis whenever the following findings are present: a recent history of asthenia, malaise, vague upper abdominal discomfort, and/or intermittent fever; absence of stigmata of chronic liver disease or splenomegaly; abnormal liver function test results (such as elevated levels of trans-aminases, gamma-glutamyl transpeptidase, and alkaline phosphatase); and a lack of specific imaging findings.

Imaging studies of inflammatory pseudotumors have revealed hypoechoic, as well as hyperechoic, masses on ultrasound. Unenhanced computed tomography images show the tumor’s hypoattenuating liver parenchyma, and contrast administration reveals variable patterns of enhancement. On magnetic resonance imaging, the lesions are typically hypointense on T1-weighted images and hyperintense on T2-weighted images, with variable enhancement patterns.

A definitive diagnosis of inflammatory pseudotumor can be made via needle biopsy findings and, occasionally, fine-needle aspiration, as long as the pathologist is aware of this possibility. In such cases, antibiotic treatment may be curative, and hepatic resection can be avoided. Corti-costeroids have been successfully used in some cases and constitute another treatment option.¹¹ Occasionally, the pseudotumor spontaneously regresses, as with the patient treated by Rosa and colleagues.¹

More data should be collected to better classify inflammatory pseudotumors and further understanding of their natural history; specific areas of future research should involve culturing the infectious agents, testing for aberrant expression of ALK-1 and its gene translocation, and testing for the expression of IgG4-positive plasma cells.

It is common practice to excise a resectable liver tumor in the absence of a firm diagnosis. However, if a preoperative diagnosis of an inflammatory pseudotumor can be made, there is no reason to advocate hepatic resection (as noted by Rosa and coworkers), as long as appropriate consideration has been given to the possible destructive nature of the lesion and the uncertainty of its potential for malignancy.¹ The case report by Rosa and associates is a good illustration of the necessity of considering the diagnosis of inflammatory pseudotumor if an atypical mass is found in the liver, particularly when it is accompanied by a clinical inflammatory process.¹ A liver biopsy is recommended to avoid unnecessary liver resection.