Mucosa-associated lymphoid tissue (MALT) lymphoma is a common low grade B-cell lymphoma arising from a background of chronic inflammatory disease at a number of mucosal sites. Those originating in the stomach are causatively linked to Helicobacter pylori infection and eradication of the bacterium with antibiotics leads to long-term complete regression of the lymphoma in ~70% of cases. Now, there is further evidence of linking Campylobacter jejuni, Borrelia burgdorferi and Chlamydia psittaci infection with immunoproliferative small intestine disease, MALT lymphoma of the skin and ocular adnexa respectively. t(11;18)/API2-MALT1, t(1;14)/IGH-BCL10, t(14;18)/IGH-MALT1 and t(3;14)/IGH-FOXP1 occur at considerably variable incidences in MALT lymphomas of different sites. The first three chromosome translocations are specifically associated with the MALT lymphoma entity and the oncogenic products of these translocations have been shown to target a common molecular pathway, i.e. the nuclear factor-κB pathway. Here, I review the recent advances in our understanding of the association of microbial pathogens with MALT lymphoma of various sites and the molecular genetics underlying the lymphoma development. [J Clin Exp Hematopathol 47(2) : 31-42, 2007]

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Radioimmunotherapy (RIT) treatment for lymphoma is a novel targeted therapeutic approach. Several years of development of radioimmunotherapeutic compounds came to fruition in February of 2002 when ⁹⁰Y-ibritumomab tiuxetan (Zevalin^TM, Y2B8) was approved in the USA and later in Europe, for the treatment of relapsed or refractory, low grade or transformed B-cell lymphoma. ⁹⁰Y-ibritumomab tiuxetan utilizes a monoclonal anti-CD20 antibody to deliver β-emitting yttium-90 to the malignant B-cells. Clinical trials have demonstrated its efficacy, which is largely independent of the intrinsic activity of the anti-CD20 antibody. A similar anti-CD20 radiotherapeutic compound, ¹³¹I-tositumomab, was subsequently approved in the USA. The advantages of increased efficacy compared to the naked antibody are gained at the expense of myelotoxicity which is dose limiting but reversible. Studies exploring expanded applications of radioimmunotherapy have been recently completed or are under way. It is hoped that RIT will be an ideal agent for consolidation after chemotherapy for both indolent and aggressive non-Hodgkin lymphoma as well as a useful addition to preparatory high dose regimens prior to transplant. RIT has been shown to be an effective and clinically relevant complementary therapeutic approach for patients with lymphoma. [J Clin Exp Hematopathol 47(2) : 43-60, 2007]

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In order to establish the method of generating powerful γδ T cells for anti-tumor immunotherapy, we investigated the effects of monocyte-derived dendritic cells (mo-DCs) on anti-tumor cytotoxicity of expanded γδ T cells. Activation of γδ T cells co-cultured for 2-3 days with immature or mature mo-DCs was evaluated by CD69 expression and anti-tumor cytotoxicity using two assays : the 5- (and 6-) carboxyfluorescein diacetate, succinimidyl ester-based cytotoxicity assay and the calcein-AM-based Terascan assay. γδ T cells were used as effector cells and myeloma cell line (RPMI8226) or chronic myelogenous leukemia blastic crisis cell line (C2F8) were used as target cells. CD69 expression on γδ T cells was enhanced by co-culture with both immature and mature mo-DCs in a cell-number-dependent fashion. CD69 expression was enhanced after addition of mo-DCs of either autologous or allogeneic origin. Activation of γδ T cells with mo-DCs enhanced anti-tumor cytotoxicity of γδ T cells against RPMI8226 and C2F8 in an effector-to-target ratio-dependent manner. Activation of γδ T cells by mo-DCs was associated with the enhancement of anti-tumor cytotoxicity of γδ T cells. Potent γδ T cells activated by mo-DCs were considered to be applicable to an efficient γδ T cell-mediated immunotherapy for tumors. [J Clin Exp Hematopathol 47(2) : 61-72, 2007]

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This report concerns a rare case of follicular lymphoma with features suggestive of primary hepatic lymphoma. At the disease onset, multiple nodular lesions in the liver and small para-aortic nodes were detected by abdominal magnetic resonance imaging without generalized lymphadenopathy. After careful observation for three months, lymphadenopathy was observed in the right occipital, para-aortic, and bilateral inguinal regions. The patient was treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) and achieved complete remission for more than 2 years. To the best of our knowledge, this is the ninth report of primary hepatic follicular lymphoma. Insufficient cases have been reported to determine the long-term outcome and clinical characteristics of primary hepatic follicular lymphoma. However, it seems that patients with primary hepatic follicular lymphoma that are treated with appropriate chemotherapy with or without surgical resection have favorable outcomes. [J Clin Exp Hematopathol 47(2) : 73-77, 2007]

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We report the case of a patient who showed spontaneous regression of bilateral conjunctival extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). A 72-year-old man underwent excisional biopsy for salmon-pink lesions involving the whole circumference of the conjunctiva in the right eye and the lower fornix in the left eye. Histopathology and immunohistochemistry showed MALT lymphoma with immunoglobulin kappa monotype shared by the lesions in both eyes. Because the patient had recurrent pulmonary tuberculosis, radiation initially planned for the large residual lesion in the right eye was postponed. Over two years, including 6 mon with anti-tuberculous treatment, the large lesion in the right eye showed spontaneous regression. The spontaneous regression of conjunctival MALT lymphoma observed in this patient suggests that following excisional biopsy for histopathological diagnosis, observation is a treatment option. [J Clin Exp Hematopathol 47(2) : 79-81, 2007]

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We report a case of a splenic inflammatory pseudotumor (myofibroblastic tumor) in a 43-year-old man with a 5-year history of chronic bronchitis and sleep apnea syndrome. The patient was hospitalized because of a screen-detected splenic mass lesion. His sputum cultures revealed Mycobacterium avium complexes on only one occasion. Imaging studies revealed a 7 cm solitary tumorous lesion, and differential diagnoses of splenic hamartoma, hemangioma, lymphoma, and angiosarcoma were obtained from the radiologist. A splenectomy followed by pathological investigations was performed. By histology, the lesion contained fibroblastic or myofibroblastic spindle cell proliferations, accompanied by variable degrees of inflammatory cell infiltration. Ziehl-Neelsen staining did not reveal acid-fast bacteria. Immunohistochemically, the fibroblastic or myofibroblastic spindle cells were positive for vimentin, human smooth muscle actin, and muscle actin, but negative for desmin, CD8, CD21, CD23, CD35, p80, Epstein-Barr virus LMP, and human herpesvirus type 8. The infiltrating lymphoid cells demonstrated a nonneoplastic pattern. The results of in situ hybridization for Epstein-Barr virus encoded RNA were negative. The postoperative course was uneventful and he has had no recurrence in 22 months. His sleep apnea syndrome and chronic bronchitis have resolved spontaneously since the splenectomy. [J Clin Exp Hematopathol 47(2) : 83-88, 2007]

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