Reactive Lymphoid Hyperplasia of the liver in a patient with colon cancer: report of two cases

Reactive lymphoid hyperplasia (RLH) is reported to occur in the gastrointestinal tract [1], skin [2], lung [3], thyroid [4], orbit [5], and pancreas [6]; however, it is very rarely reported in the liver. To the best of our knowledge, only 12 cases with RLH of the liver have so far been reported in the English literature [7‐15]. RLH is thought to represent an immune-mediated reactive phenomenon, and very few cases may arise in association with malignant tumor. But, there are no reports mentioned about the relationship between RLH and malignant tumor. Our two cases were the first report of RLH of the liver accompanying colon cancer. So we report two cases of RLH of the liver accompanying colon cancer and discuss its morphological features.

Reactive lymphoid hyperplasia is recognized as a region that is well demarcated and characterized by hyperplastic lymphoid follicles with reactive germinal centers, which consist of polymorphic and polyclonal cell populations and aggregations of mature lymphocytes, plasma cells, and other types of inflammatory cells [12]. In the liver, these reactive lesions have been variously termed RLH, nodular lymphoid lesions [14], and pseudolymphoma. These lesions are very rare, and they appear clinically to indicate the same disease. We decided to use the term "RLH of the liver" because this most closely reflects the pathological features of the disease. However, the term "pseudolymphoma" is problematic because it indicates a low-grade type of MALT lymphoma. Since malignant transformation is reported in this type of MALT lymphoma, surgical resection is indicated. Therefore, even when pseudolymphoma is diagnosed preoperatively, some patients have undergone resective surgery [13]. In contrast, as RLH is not considered to have malignant potential, therapeutic strategies are totally different from those for low-grade MALT-type lymphoma. We therefore believe it is necessary to eliminate the ambiguous term "pseudolymphoma" and clearly differentiate RLH from low-grade MALT-type lymphoma. Some past studies have also advocated this approach to classification, and Sharifi and colleagues [14] have proposed clear diagnostic criteria. Immunohistological and genetic tests to ascertain whether infiltrating lymphocytes are monoclonal or polyclonal enable differentiation of RLH from low-grade MALT-type lymphoma.

By previously reported cases, in terms of imaging findings, RLH of the liver is depicted as a hypoechoic lesion on ultrasound and as a low-density lesion on plain CT, but contrast CT findings vary. Both MRI T1-low and T2-high intensity images yield the same results, and angiography shows hypervascularity. In our patients, results of preoperative diagnostic imaging conformed to this pattern; i.e. low-echo and plain CT demonstrated a low-density lesion, while contrast CT showed mild enhancement. Moreover, on equilibrium phase of contrast CT in the first patient, the area around RLH was depicted as a high-density area, possibly indicating a capsule. The present study was the first to conduct contrast SPIO-enhanced MRI in hepatic RLH. No SPIO uptake into the mass occurred, and the boundary with the normal liver was very clear. The further discussion of such rare cases based on the imaging findings including SPIO-enhanced MRI will provide more information about this rare entity. But, at this point in time, it is very difficult to completely rule out malignancies such as HCC, metastatic liver tumors, or malignant lymphomas based solely on diagnostic imaging findings. Ultimately, preoperative biopsy is therefore an essential diagnostic tool.

While the cause of RLH has not been clarified, most patients are middle-aged or elderly women. In terms of underlying diseases, various chronic inflammatory diseases, such as chronic hepatitis, Sjogren's syndrome, chronic thyroiditis, and primary biliary cirrhosis, have been confirmed. Hence, autoimmune mechanisms are most likely involved. In our cases, the patients were a middle-aged woman and lymphoid infiltration was observed in the portal area around the nodule, suggesting a similar mechanism. However, lymphoid infiltration was confined to the area around the nodule, the rest of the hepatic parenchyma was normal, and hepatitis virus markers were negative, suggesting that this lesion was local rather than diffuse. Furthermore, as systemic immunologic abnormalities were not detected, our cases did not appear to be associated with systemic autoimmune disease. Including the present patients, five cases of hepatic RLH accompanying malignancies have been reported [8, 11, 15], some of which had asynchronous onset, but the present study is the first to report RLH of the liver accompanying colon cancer. Because there are a very few cases, so it is not clear whether the malignancies were involved in the onset of RLH. Furthermore, characteristic imaging findings or morphological features in these patients were not detected. But we believe that new factors involved in the onset mechanism of RLH may be identified by carefully monitoring the clinical course of our two patients.

In summary, we report two cases of RLH of the liver in a patient with colon cancer. RLH of the liver is extremely rare and it is very difficult to think of RLH of the liver as differential diagnosis.