Inflammatory Pseudotumor Resembling a Malignant Pancreatic Disease Process

Discussion

Inflammatory pseudotumors comprise a challenging diagnosis, and thus it is vital to keep this diagnosis in mind when a patient presents with a soft tissue tumor. However, inflammatory pseudotumors can be difficult to distinguish from other soft tissue lesions, and thus, the differential diagnosis can be rather extensive.

It is unclear what causes inflammatory pseudotumors, although it seems that they can be related to both acute and chronic inflammation, autoimmune processes, trauma, surgery, infection, another related malignancy, and IgG4-related disease processes (1, 2). Often, immunohistochemical staining involving T cells and B cells can aid in differentiating between the diagnosis of inflammatory pseudotumor and lymphoma. In an inflammatory pseudotumor, both T cells and B cells are present, compared to lymphoma, where either T cells or B cells will dominate the population of cells (1, 2). A multitude of organisms have been associated with inflammatory pseudotumors, such as Epstein-Barr virus, actinomycetes, mycoplasma, nocardiae, as well as many others (1, 2, 3). Some of the characteristics of inflammatory pseudotumors, such as fever, anemia, thrombocytosis, weight loss, among others, are associated with interleukins and cytokines, which produce the systemic effects seen throughout the body (1, 2).

Many studies have demonstrated that inflammatory pseudotumors with certain histology can predict how aggressively the tumor will behave. Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that has been found to be over-expressed in half of inflammatory pseudotumors, leading to a neoplastic process (2). A study by Coffin et al. showed that tumors lacking ALK positivity were associated with an older age and distant metastasis (not local recurrence); patients may die from the disease, thus advocating that ALK expression in these tumors may be a marker of a more favorable prognosis (2, 4). A study by Mariño-Enriquez et al. reported that a specific ALK staining pattern in the nuclear membrane of inflammatory myofibroblastic tumors was correlated to rapid local recurrence and decreased mortality, suggesting a more aggressive behavior and less favorable prognosis in this subset of patients (2, 5). Thus, testing for the presence of ALK may be beneficial in patients with inflammatory pseudotumors.

An inflammatory pseudotumor can present in practically any location in the body, although the most common sites involve the orbit or the lungs (1, 2). Inflammatory pseudotumors can involve the gastrointestinal tract, albeit rare, with gastric and ileocecal lesions being most commonly located in the gastrointestinal tract (2, 6). Radiographic imaging is a vital diagnostic component for these patients. These tumors can be difficult to be distinguished on radiographic imaging due to the variability and non-specific appearance. Inflammatory pseudotumors can be either hyperechoic or hypoechoic, have variable borders on ultrasound, show high to low attenuation in comparison to the surrounding structures on CT scan, demonstrate heterogeneous or homogeneous features, and variable signal intensity with T1-weighted and T2-weighted images on MR imaging (1, 2, 7-10). Inflammatory pseudotumors of the pancreas, liver, and stomach can reveal calcification on imaging as well. With identification of these imaging characteristics, it is critical for differential diagnosis (1).

As discussed previously, the treatment is usually surgical resection, if feasible. However, other treatment modalities include radiation, steroids, nonsteroidal anti-inflammatory drugs, and even in some cases, chemotherapy (1, 2, 6, 11). Recently, studies revealed that pediatric patients with inflammatory myofibroblastic tumors can have improved outcomes with treatment involving either neoadjuvant or adjuvant ALK inhibitors. Inflammatory myofibroblastic tumors, a subset of inflammatory pseudotumors, have the capacity of carrying ALK translocations that hold the ability to respond to these tyrosine kinase inhibitors. This therapy can be utilized as definitive therapy in certain cases, or as supplementation to surgical resection in others (12). A study by Brivio et al. in 2019, involving two separate cases of inflammatory myofibroblastic tumors, demonstrated utilization of and treatment response to Ceritinib, a second-generation tyrosine kinase inhibitor, for the treatment of inflammatory myofibroblastic tumors. One of the two patients underwent sole treatment with the ALK inhibitor, while the second patient underwent Ceritinib treatment leading to a 70% reduction in the size of the tumor, and subsequent complete surgical resection (13). Again, this highlights the usefulness of testing for ALK in patients with inflammatory pseudotumors and may help direct treatment regimens. The estimated rate of recurrence for inflammatory pseudotumors is between 18-40% (2, 6). Upon recurrence, surgical resection may continue to be the treatment modality of choice given that transformation to a malignancy has been reported (6, 14).

Inflammatory pseudotumor is a challenging diagnosis and thus, is quite important to keep it in mind while making a differential diagnosis for a patient who presents with nonspecific symptoms and a mass on imaging. Clinically and radiographically, these tumors can mimic malignant disease processes (1). Therefore, surgeons should be knowledgeable on the necessary workup and treatment modalities for this patient population.