IgG4-associated disease (IgG4-RD) is an autoimmune disease in nature, but it has unique clinicopathological features. IgG4-RD is a systemic fibrotic inflammatory disease involving multiple organs, as it is often characterized by the formation of “tumor like” damage, and is characterized by elevated serum IgG4 levels. The histopathological features of the disease are fibrosclerotic lesions with dense lymphoplasmacytic infiltration, mostly IgG4-positive plasma cells (i.e., the proportion of IgG4+ plasma cells to IgG+ plasma cells is increased), along with eosinophilic infiltration and occlusive phlebitis. Wensheng Wang, Department of Hematology, Peking University First Hospital Recently, the relationship between IgG4-RD and malignancies has received increasing attention, and cases of IgG4-associated autoimmune pancreatitis with pancreatic cancer accompanying or occurring sequentially have been reported. Lymphoma and IgG4-RD are both “lymphatic tissue proliferation”, but the former is essentially “clonal (tumorigenic) proliferation of lymphatic tissue” and the latter is essentially “reactive (inflammatory) proliferation of lymphatic tissue”. “The two seem to be more closely related. This is also true, as there have been several reports from abroad on cases of lymphoma associated with IgG4-RD, with pathological types involving diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma, follicular lymphoma, small lymphocytic lymphoma, and mesenchymal large cell lymphoma (ALCL). The sequence of lymphoma and IgG4-RD is inconsistent, as lymphoma may occur before IgG4-RD or during the clinical follow-up period after IgG4-RD has been diagnosed, or it may be detected at the same time as IgG4-RD. In one particular case, DLBCL, IgG4-RD, and ALCL were diagnosed successively, i.e., two histopathologically distinct lymphomas occurred successively in IgG4-RD. The correlation between lymphoma and IgG4-RD is obvious, and 111 patients diagnosed with IgG4-RD were followed for several years, and three cases were found to have developed lymphoma later, which leads to the inference that Patients with IgG4-RD are at a significantly higher risk of developing lymphoma. Although the mechanism of lymphoma development in IgG4-RD patients is not resolved, it is well known that patients with autoimmune diseases such as dry syndrome and Hashimoto’s thyroiditis are prone to lymphoma development. The mechanism is presumed to be the presence of abnormal regulation of B lymphocytes in autoimmune diseases, which leads to abnormal proliferation of B lymphocytes and ultimately to the formation of lymphoma. Mitsui et al. reported a case in which IgG4-RD was diagnosed 10 years after the diagnosis of diffuse large B-cell lymphoma and chemotherapy, and re-immunohistochemical analysis of the lymph node biopsy specimens from that year revealed the presence of many IgG4-positive plasma cells around the DLBCL damage, so it was hypothesized that the patient had a subclinical type of IgG4-RD before the development of DLBCL, because at that time there was no It was not diagnosed because the concept of “IgG4-RD” had not been developed at that time, and then it gradually progressed to clinical IgG4-RD. In our case, the patient was diagnosed with “diffuse small lymphocytic lymphoma” by biopsy 17 years ago due to enlarged lymph nodes. Although the diagnosis was later rejected by the pathology departments of several hospitals, the diagnosis of IgG4-RD was later confirmed, and eventually DLBCL occurred, which makes us wonder whether the diagnosis of “diffuse small lymphocytic lymphoma” could really be overturned, given the difficulty and complexity of lymphoma diagnosis, or whether the diagnosis of IgG4-RD might have been made at that time. IgG4-RD may have existed at that time (the manifestation of “lymphoid hyperplasia” may be the manifestation of IgG4-RD), and since IgG4-RD responds well to glucocorticoids, the combination chemotherapy regimen containing glucocorticoids is effective, if we can obtain the lymph node tissue specimens at that time, we can confirm whether IgG4-RD existed at that time by immunohistochemistry. If IgG4-RD was present at that time, we can then describe the clinical course of the patient, namely: lymphoid hyperplasia, probably IgG4-RD or B-cell hypermalignant lymphoma (inert lymphoma), which appeared 17 years ago and went into remission after glucocorticoid-containing combination chemotherapy regimen and autologous peripheral blood HSCT. Years later, IgG4+ lymphocytes and plasma cells proliferated again, leading to the diagnosis of IgG4-RD, while the disease progressed to DLBCL. The diagnosis of this patient gives us the following tips: (1) IgG4-RD is closely related to the development of lymphoma and is a predisposing factor for lymphoma, and patients with IgG4-RD should be followed up for a long time to be alert for the development of lymphoma. (2) IgG4-RD and lymphoma are both “lymphoid tissue proliferation”, and their clinical manifestations are similar and easy to be confused, and biopsy pathology of lesions combined with immunohistochemistry is the “gold standard” for diagnosis and differentiation.