Primary splenic and nodal marginal zone (MZ) lymphomas are rare small B cell lymphomas presenting with similar histopathologic features. The neoplastic cell population mostly consists of monocytoid B cells organized in a MZ pattern, associated with centrocytoid cells colonizing follicles. About 50% of cases have a monotypic plasma cell component. The different histopathologic patterns and differential diagnosis are discussed here. Both diseases share a similar immunophenotype, with the expression of B-cell associated antigens and restriction of immunoglobulin light chain. The only difference is the more frequent expression of IgD in splenic than in nodal lymphomas. The most recent findings in genetics and molecular biology are presented and discussed. The main clinical and biological symptoms are described and the similarity of some cases with Waldenströms macroglobulinemia is stressed. Both lymphomas present with the same type of bone marrow involvement with a high frequency of intravascular infiltrates, which can be associated with interstitial and nodular infiltrates. Transformation into diffuse large B cell lymphoma occurs in about 10 to 15% of the cases. The outcome in many splenic MZ lymphomas is characterized by a lengthy survival after splenectomy (9 to 13 years or longer), despite the absence of a consensus on the optimal treatment. Nodal MZ lymphoma has a more aggressive evolution and seems to only be curable at an early stage. Further studies are needed of both lymphomas to improve treatment and prognosis.
Nuclear factor-κB (NF-κB) is a family of highly regulated dimeric transcription factors that play pivotal roles in inflammatory responses and immunological reactions. Although they are often activated concurrently, classical and alternative NF-κB activation pathways have distinct regulatory functions, producing secondary inflammatory responses and regulating lymphoid organ development, respectively. As NF-κB functions in the proliferation, differentiation, and survival of lymphocytes, increased activation also participates in the oncogenesis of many lymphoid malignancies. Aberrant NF-κB activation in these tumor cells results from genetic changes or the activation of NF-κB pathways by indirect mechanisms. Recent observations have suggested that NF-κB provides many of the requirements for cellular transformation. Bcl-3, a member of the IκB family, is overexpressed in t (2 ; 5)+ anaplastic large cell lymphoma due to genetic and epigenetic alterations. The different contributions of the classical and alternative NF-κB pathways to tumorigenesis, however, are not well understood. The clinical importance of NF-κB is also being recognized, with the approval of the NF-κB inhibitor bortezomib for treatment of advanced multiple myeloma. A better understanding of the molecular pathways involving NF-κB will surely contribute to more sophisticatedly targeted treatments for malignancies in the future.
We have previously demonstrated that the CCR7 ligands, CCL19 and CCL21, rapidly induce vigorous endocytosis in mature murine dendritic cells (DCs). The mechanisms underlying the enhanced endocytosis, however, have remained elusive. In the present study, we examined effects of CCL19 and CCL21 on the organization of the actin cytoskeleton in murine DCs. These chemokines considerably increased the intracellular level of fibrous actin and induced the formation of large petal-like ruffles of actin filaments in mature DCs. In addition, a robust network of interconnected ruffles of actin filaments was assembled at the periphery of the cells after stimulation with the chemokines. The actin-related protein (Arp) 2/3 complex has been implicated in the formation of fibrous actin structures. During cytoskeletal reorganization, Arp2/3 complexes co-localized with the interconnected ruffles at the cell periphery. Thus, the Arp2/3 complex seems to be involved in CCR7 ligand-induced actin reorganization in mature DCs. The time course of the CCL19-induced actin-reorganization corresponded to that of the endocytic activity. In the presence of cytochalasin D, an actin polymerization inhibitor, CCL19 failed to induce endocytosis and the interconnected ruffles did not form in mature DCs. Thus, CCR7-induced actin assembly may be part of the endocytic process in mature DCs.
A 58-year-old Japanese man developed discomfort of his left neck, gradually increasing left chest pain, and weight loss (15 kg over six months). His primary physician noted generalized lymphadenopathy, and a neck lymph node was excised for diagnosis. When he was admitted to our hospital, he had severely decreased appetite accompanied by a large intra-abdominal mass. The lymphadenopathy was temporarily reduced by CHOP (cyclophosphamide, hydroxydoxorubicin/adriamycin, vincristine/oncovin, prednisone) chemotherapy, but pancytopenia and hepatomegaly persisted. After 3 courses of therapy, tumor cell regrowth was evident in peripheral blood and bone marrow and his course rapidly declined, with complications from hemophagocytic syndrome. He expired after a total course of 6 months. A postmortem examination was performed 2 hours after death. A final diagnosis of interdigitating cell sarcoma was made based on histological and immunohistochemical analyses of the biopsied lymph nodes and autopsy materials. His clinical course was extremely aggressive, and chemotherapy was not effective. Discussion of this case provides important insight into the clinicopathological features and treatment of this neoplasm.
We explored two cases of CD20-positive cytotoxic T cell lymphoma, a gastric lymphoma and an intestinal lymphoma. Neoplastic cells of the gastric lesion, possessing small cleaved-like nuclei with dense nuclear chromatin, infiltrated the mucosa in association with disappearance of the gastric glands. Neoplastic cells of the intestinal case had large, round nuclei with conspicuous nucleoli, with ulceration of intestinal surface membrane. In both cases, the neoplastic cells exhibited CD3+, CD4-, CD8+, CD20+, CD79a-, perforin+, granzyme B+, TIA-1+ phenotypes. Neoplastic cells of the intestinal lesion also demonstrated positive reactivity for CD56. The gastric lymphoma was initially diagnosed as an extranodal marginal zone B-cell lymphoma, due to morphological similarity to gastric MALT lymphomas and CD20 positivity. Thus, CD20 expression on neoplastic cells in T cell lymphoma may complicate accurate diagnosis. In this report, we review previously reported CD20-positive T cell lymphoma cases, reinforcing our suggestion that recognition of this type of CD20+ lymphoma is important in making a correct diagnosis and providing adequate therapy for patients.