IgG4-Related Lymphadenopathy

Lymphadenopathy is frequently observed in patients with immunoglobulin G4-related disease (IgG4-RD) and sometimes appears as the first manifestation of the disease. The diagnosis of IgG4-related lymphadenopathy is complicated owing to a great histological diversity, with at least 5 histological subtypes. Indeed, lymph node biopsy may be performed under the suspicion that the lymphadenopathy is a malignant lymphoma or other lymphoproliferative disorder. The diagnosis of IgG4-RD is characterized by both elevated serum IgG4 (>135 mg/dL) and histopathological features, including a dense lymphoplasmacytic infiltrate rich in IgG4+ plasma cells (IgG4+/IgG+ plasma cell ratio >40%). However, patients with hyper-interleukin (IL-) 6 syndromes such as multicentric Castleman's disease, rheumatoid arthritis, and other immune-mediated conditions frequently show lymph node involvement and often fulfill the diagnostic criteria for IgG4-RD. Owing to these factors, IgG4-RD cannot be differentiated from hyper-IL-6 syndromes on the basis of histological findings alone. Laboratory analyses are crucial to differentiate between the 2 diseases. Hyper-IL-6 syndromes are characterized by elevated serum levels of IgG, IgA, IgM, and C-reactive protein (CRP); thrombocytosis; anemia; hypoalbuminemia; hypocholesterolemia. In contrast, IgG4-RD does not share any of these characteristics. Therefore, the diagnosis of IgG4-RD requires not only pathological findings but also clinical and laboratory analyses

Differential diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma and other indolent lymphomas, including mantle cell lymphoma

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) accounts for approximately 1% of all lymphomas in our department. In this article, we describe the differential diagnosis of CLL/SLL from other indolent lymphomas, with special reference to follicular lymphoma, marginal zone B-cell lymphoma, lymphoplasmacytic lymphoma, and mantle cell lymphoma, although the latter is considered to be aggressive. CLL/SLL often exhibits proliferation centers, similar to follicular lymphoma. Immunohistological examination can easily distinguish these two lymphomas. The most important characteristic of CLL/SLL is CD5 and CD23 positivity. Mantle cell lymphoma is also CD5-positive and there are some CD23-positive cases. Such cases should be carefully distinguished from CLL/SLL. Some marginal zone lymphomas are also positive for CD5 and such cases are often disseminated. Lymphoplasmacytic lymphoma should also be a differential diagnosis for CLL/SLL. It frequently demonstrates MYD88 L265P, which is a key differential finding. By immunohistological examination, the expression of lymphoid enhancer-binding factor 1 is specific for CLL/SLL and can be a good marker in the differential diagnosis

A review of EBV-positive mucocutaneous ulcers focusing on clinical and pathological aspects

Epstein-Barr virus (EBV)-positive mucocutaneous ulcers (EBVMCUs) were first described as a lymphoproliferative disorder in 2010. Clinically, EBVMCUs are shallow, sharply circumscribed, unifocal mucosal or cutaneous ulcers that occur in immunosuppressed patients, including those with advanced age-associated immunosenescence, iatrogenic immunosuppression, primary immune disorders, and HIV/AIDS-associated immune deficiencies. In general, patients exhibit indolent disease progression and spontaneous regression. Histologically, EBVMCUs are characterized by the proliferation of EBV-positive, variable-sized, atypical B-cells. According to conventional histopathologic criteria, EBVMCUs may diagnosed as lymphomas. However, EBVMCUs are recognized as pseudomalignant lesions because they spontaneously regress without anti-cancer treatment. Therefore, overtreatment must be carefully avoided and multilateral differentiation is important. In this article, we reviewed previously reported EBVMCUs focusing on their clinical and pathological aspects in comparison with other EBV-positive B-cell neoplasms

Detection of oncogene rearrangements in human non-Hodgkin's lymphomas.

Southern blot hybridization was used to detect the rearrangement and amplification of five proto-oncogenes (bcl-2, bcl-1, c-myc, c-myb and c-Ha-ras) and one tumor suppressor gene (RB-1) in 55 Japanese patients with non-Hodgkin's lymphoma; 16 with T-cell lymphomas and 39 with B-cell lymphomas (7 follicular and 32 diffuse lymphomas). Genetic abnormalities of the proto-oncogenes were detected in 7 of the 55 (13%). Genetic abnormalities of bcl-2 plus other genes were detected in 5 of 7 cases of follicular lymphoma (71%), rearrangements of bcl-2 and c-myc, rearrangement of bcl-2 and amplification of c-myb. Genetic abnormalities were observed in only three cases of diffuse lymphoma. In each of 3 cases of B-cell lymphoma, one of the genes, blc-2 mbr, bcl-2 mcr and c-myc, was rearranged respectively. The incidence of genetic abnormalities in diffuse lymphomas (6.3%) was lower than that in follicular lymphomas. None of diffuse lymphomas had double oncogene abnormality. No abnormalities were found in RB-1, bcl-1, and Ha-ras. These findings suggest that follicular lymphomas are associated with some abnormalities of oncogenes not restricted to bcl-2 that facilitate growth which may be associated with their clinical features.</p

A Case of Myoepithelial Hamartoma: Morphological Variation Supported by OCT4 Expression

In this report, we describe a patient with myoepithelial hamartoma, which is regarded as synonymous with adenomyosis and heterotopic pancreas. Endoscopy revealed a submucosal tumor in the antrum of the stomach. Subsequently, distal gastrectomy with Roux-en-Y reconstruction was performed. Histological findings of adenomyomatous lesion and heterotopic pancreatic tissue were observed in this lesion. The distribution of OCT4, which is a pluripotency marker, varied in each part

Expression of thyroglobulin on follicular dendritic cells of thyroid mucosa-associated lymphoid tissue (MALT) lymphoma

Reportedly, thyroid mucosa-associated lymphoid tissue (MALT) lymphoma is closely associated with Hashimoto's thyroiditis. However, it remains unknown which antigen is closely associated with thyroid MALT lymphoma. We examined whether B cell response to thyroglobulin (Tg), which is a common thyroid-specific autoantigen, is related etiologically to the pathogenesis of thyroid MALT lymphoma. Expression of human Tg antigens and Cluster of differentiation (CD) 35 was examined immunohistochemically in 15 cases of thyroid MALT lymphoma using paraffin-embedded, formalin-fixed tissue specimens. In all cases of thyroid MALT lymphoma, human Tg was detected immunohistochemically in the follicular epithelial cells and follicular dendritic cells (FDCs). These FDCs were positive by double immunostaining for anti-human Tg rabbit polyclonal antibody (Ab) and for CD35. Results showed that the Tg, a thyroid autoantigen, had immunostained the germinal center of the thyroid MALT lymphoma. The Tg was present in the FDCs, as revealed by the staining pattern of the germinal center;this fact was confirmed by double immunostaining of anti-human Tg mouse monoclonal Ab and anti-CD35 mouse monoclonal Ab. The results of our study suggest that Tg is an autoantigen that is recognized by thyroid MALT lymphoma cells.</p