Micronodular T-cell/histiocyte-rich B-cell Lymphoma In Spleen: Study Of The Immunophenotype And Gene Rearrangement

【Background】Lymphoma is a type of cancer that originates from lymph nodes or extranodal lymphoid tissues. Histologically, it is distinguished by the neoplastic proliferation of lymphocytes. In clinic, it often presents with lymphadenectasis, and spleen involvement is commonly found in most cases. Splenic lymphoma is a kind of malignant tumor in spleen, which can be primary or consequent from other diseases. The lesion of lymphoma in spleen can be either diffuse small nodules, multi-mass or single huge mass. Due to histopathological features, lymphoma can be divided into Hodgkin lymphoma and non-Hodgkin lymphoma, which can be both involved in spleen. It has great importance to make accurate diagnosis of splenic lymphoma by the histological characteristics and immunophenotype.T-cell/histiocyte-rich B-cell lymphoma (T/HRBCL) is an uncommon morphologic variant of diffuse large B-cell lymphoma (DLBCL). Pathologi- cally, it is distinguished by <10% malignant B cells amid a majority population of reactive T lymphocytes and histiocytes. In clinic, T/HRBCL occurs at a younger age with a median age in the fourth decade of life. A male predomin -ance has been noted in most series. Most series suggest that T/HRBCL infiltrate the spleen, liver, and bone marrow. T/HRBCL patients also appear more likely to develop"B"symptoms such as explained fever >38℃, drenching night sweats, and unexplained weight loss >10% of body weight over a 6-month period. Primary T/HRBCL in spleen is very rare, and the diagnosis should consider the immnuphenotype and gene rearrangement besides the typical morphological features.【Objectives】1. To retrospect 20 cases of primary splenic lymphoma from 1999-2008;2. To investigate a very special case of HCV infected T-cell/histiocyte-rich B-cell lymphoma (THRBCL) with anaplastic large cell lymphoma (ALCL)-like differentiation in spleen and study the pathological phenotype.【Methods】1. To categorize the 20 cases of lymphoma according to WHO classification;2. To analyze the immunophenotype of the tumor cells by EnVision immunohistochemical staining;3. To investigate the clonality of tumor cells by gene rearrangement analysis, including extracting the DNA from the tissues and doing PCR with specific primers of Ig gene and TCR gene;4. Further study of the origin of the tumor cells by employing laser capture microdissection (LCM).【Results】1. According to WHO (2001) classification of lymphoma, in the 20 cases, there were two cases of peripheral T cell lymphoma, one case of anaplasitc large cell lymphoma, eight cases of large B cell lymphoma, four cases of lymphoplasmacytoid lymphoma, two cases of marginal zone lymphoma, one case of follicular lymphoma and one case of small lymphocytic lymphoma. Besides, there was another special case characterized as T cell/histiocyte rich B cell lymphoma, of which the morphology, immunophenotype and gene rearrangement were unusual and further studies were done with it.2. The morphology, immunophenotype and gene rearrangement of the special case were presented as follows:1) Morphologically, a great many of small lymphocytes and some histiocytes mingled with scattered anaplastic large cells, of which the cytoplasm was basophil and the nuclei were large and kidney-shaped with remarkable perinucleal halo;2) On immunohistochemical analysis, the large cells were positive for CD20, EMA, CD30, but negative for ALK. The background cells were composed of predominant CD3-positive small T lymphocytes, and some CD20-positive small B lymphocytes as well as CD68-postive histiocytes;3) In gene rearrangement, only IGK was positive, which suggested that the tumor cells be originated from B cell.4) The results of LCM indicated that CD20-positive small B lymphocytes were the real tumor cells.【Conclusions】1. Most of the splenic primary lymphomas are B-cell lymphoma, especially the large B-cell lymphoma;2. According to the WHO classification, T/HRBCL is an uncommon morphologic variant of DLBCL; however, for this case of splenic primary T/HRBCL, a micronodular pattern of splenic infiltration is a recognized feature, and some of the large cells are anaplastic large cell-like. On immunohistochemical analysis, the background small lymphocytes express predominately CD3. Most importantly, the small B lymphocytes are neoplastic, which is different from the descripton of T/HRBCL in WHO classification. Whether T/HRBCL is a new subtype of lymphoma needs to be concerned;3. The patient has been infected with HCV since childhood, which suggests the infection of HCV may play a role in the pathogenesis of the lymphoma.