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The diagnosis of marginal zone lymphomas (MZL) is challenged by the lack of specific markers that distinguish them from other low-grade non-Hodgkin B-cell lymphomas. Myeloid cell nuclear differentiation antigen (MNDA) is a nuclear protein that labels myelomonocytic cells as well as B lymphocytes that localize to the marginal zone areas of splenic white pulp. We evaluated MNDA expression in a large series of B-cell lymphomas to assess the sensitivity and specificity of this antigen for the characterization of MZL. A total of 440 tissue sections containing extramedullary B-cell lymphomas and 216 bone marrow biopsies containing atypical or neoplastic lymphoid infiltrates were stained for MNDA by immunohistochemistry. Among the extramedullary lymphoma cases, approximately 67% of nodal MZL, 61% of extranodal MZL, and 24% of splenic MZL expressed MNDA. MNDA was also infrequently expressed in other B-cell neoplasms including mantle cell lymphoma (6%), chronic lymphocytic leukemia/small lymphocytic lymphoma (13%), follicular lymphoma (FL) (4%), lymphoplasmacytic lymphoma (25%), and diffuse large B-cell lymphoma (3%). In contrast, MNDA was only expressed in 2.3% of all bone marrow biopsies involved by lymphoid infiltrates, including 2 cases of FL and one case of MZL. Collectively, these data support the inclusion of MNDA in the diagnostic evaluation of extramedullary B-cell lymphomas, particularly those in which the differential diagnosis is between low-grade FL and MZL., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We describe 4 patients aged 62 to 79 years with splenomegaly and bone marrow involvement by splenic B-cell lymphoma who developed more than 55% prolymphocytes in blood. The diagnosis of B-cell prolymphocytic leukemia was considered clinically based on a markedly elevated leukocyte (up to 131.5×10(9)/L) or prolymphocyte (up to 86%) count. Splenectomy was performed in all patients, and spleen weight ranged from 1500 to 2380 g. In 3 patients, the neoplasms were classified as splenic marginal zone lymphoma, and in 1 patient, the neoplasm was classified as splenic diffuse red pulp small B-cell lymphoma. In 2 patients, splenectomy preceded a B-cell prolymphocytic leukemia-like picture, and the spleen showed splenic marginal zone lymphoma or splenic diffuse red pulp small B-cell lymphoma with increased (10%-20%) nucleolated cells consistent with prolymphocytes. In the other 2 patients, a B-cell prolymphocytic leukemia-like picture prompted splenectomy. Initial examination of bone marrow in these patients suggested splenic marginal zone lymphoma. The spleen specimens showed extensive involvement by splenic marginal zone lymphoma with numerous prolymphocytes. Flow cytometry immunophenotyping in all cases showed lymphocytes positive for monotypic surface immunoglobulin (bright), pan-B-cell antigens, CD11c, CD22, and FMC7. Immunohistochemical analysis in all patients showed moderate to bright p53 expression in the spleen (n=3) or bone marrow (n=2). Annexin A1 and cyclin D1 were negative in all cases. Conventional cytogenetic analysis showed del(7q) in 3 patients. We conclude that splenic B-cell lymphoma of various types can undergo prolymphocytoid transformation with more than 55% prolymphocytes in the blood mimicking B-cell prolymphocytic leukemia., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a B-cell neoplasm that is typically CD5 negative. We describe the clinicopathologic, immunophenotypic, and cytogenetic features of 14 cases of CD5+ MALT lymphoma. There were 9 men and 5 women (median age, 68 years; range, 34-87 years). MALT lymphoma was initially diagnosed in salivary glands (n = 4), nasopharynx (n = 2), and 1 case each in conjunctiva, thyroid, stomach, colon, skin, lung, kidney, and retroperitoneum. Two patients had localized disease; 9 had disseminated disease with generalized lymphadenopathy (n = 8), multifocal lymphoma (n = 6), or bone marrow involvement (n = 5). No staging information was available for the remaining patients. None presented with B symptoms, splenomegaly, cytopenias, lymphocytosis, monoclonal gammopathy, or elevated serum lactate dehyrogenase. Serum β2-microglobulin was elevated in 6. Morphologically, the neoplasms had features typical of MALT lymphoma being composed of small- to medium-sized cells with round to slightly irregular nuclear contours and moderate amount of cytoplasm. Lymphoepithelial lesions were noted in 4 cases. CD5 was positive in all cases by immunohistochemistry (n = 12) and/or flow cytometry (n = 11). All cases assessed were negative for cyclin D1 (13/13) and CD10 (11/11). Conventional cytogenetics in 7 cases showed trisomy 3 in 3 and diploid in 4. With a median follow-up of 71 months (range, 2-131 months), overall survival at 5 years was 100%, although 5 patients required chemotherapy. Our results show that CD5 expression is rare in MALT lymphoma, and is often associated with nongastric disease and an increased tendency to present with disseminated disease. Overall survival is excellent with appropriate therapy., (Published by Elsevier Inc.)

Inhibition of apoptosis seems to play an important role in the pathogenesis of marginal zone lymphoma. Apoptosis regulator B-cell lymphoma 10 (BCL10) may show aberrant nuclear localization in some aggressive extracutaneous MALT lymphomas, often in association with a MALT1 gene t(11;18)(q21;q21) translocation. The possible occurrence of this association in primary cutaneous marginal zone lymphoma (PCMZL) remains insufficiently explored. The aim of this study was to evaluate BCL10 protein expression pattern and its possible relationship to the presence of t(11;18)(q21;q21) and other MALT1 gene abnormalities in PCMZL and to assess their clinical significance. The study included 42 consecutive PCMZL patients diagnosed on the basis of the World Health Organization/European Organization for the Research and Treatment of Cancer classification criteria. BCL10 expression was immunohistochemically evaluated in all cases, whereas t(11;18)(q21;q21) reverse transcriptase polymerase chain reaction amplification was performed on 21 samples. In addition, the presence of other MALT1 gene translocations was explored in 26 samples by interphase fluorescence in situ hybridization using a MALT1 locus-specific probe. We observed the presence of aberrant nuclear BCL10 expression in a significant number of PCMZL cases (36%, 15/42). This aberrant expression was significantly related to the development of extracutaneous disease. In contrast, neither the t(11;18)(q21;q21) translocation nor other MALT1 gene translocations could be demonstrated. t(11;18)(q21;q21), strongly linked to extracutaneous MALT lymphomas, does not seem to play a role in PCMZL. The participation of other MALT1 gene translocations in PCMZL pathogenesis seems also unlikely.

We report the first case of primary mucosa-associated lymphoid tissue (MALT) lymphoma of the vagina, the diagnosis of which is supported by genetic and immunophenotypic studies. A 65-year-old, para 2 woman presented to our hospital in July 1997 with a history of prolonged vaginal discharge. Although cytologic examination suggested possible malignancy, a biopsy of the vaginal wall was diagnosed as chronic inflammation. In June 2000, she underwent gynecologic examination because of anuria. Excisional biopsy revealed subepithelial infiltration of atypical lymphoid cells that stained for CD20, CD79a, and BCL-2; stained weakly for IgM; and did not stain for CD3, CD5, CD7, CD10, CD56, CD23, and IgD, suggesting marginal zone B-cell lineage. Monoclonality was detected by Southern blot analysis, and this patient was finally diagnosed as having primary MALT lymphoma of the vagina. She received 3 cycles of chemotherapy (THP-COP) and concurrent radiation to the whole pelvis. The patient is alive and well 40 months after treatment. Because the vagina is one of the mucosa-associated tissues, MALT lymphoma, though rare, must be included in the differential diagnosis of the vaginal neoplasms.

We describe an 87-year-old female patient presenting with a breast lump and axillary lymphadenopathy. Histological examination revealed the lump to be a CD5-positive extranodal marginal zone B-cell lymphoma (MZBCL) of mucosa-associated lymphoid tissue. Subsequent staging revealed disseminated disease including the head and neck region. Only 2 cases of CD5-positive MZBCL have undergone any form of cytogenetic analysis, and we report the first standard karyotype of such a case. This revealed partial trisomy 3,7q deletion and an additional marker chromosome. Notably, cells lacked the t(11;14) found at high frequency in mantle cell lymphoma and trisomy 12 found in B small lymphocytic lymphoma (B-SLL). These results, combined with the clinical, histological, and immunophenotypic picture, suggest a marginal zone origin for the neoplastic lymphocytes, rather than a relationship with mantle cell or small lymphocytic lymphoma.

A case of synchronous adenocarcinoma of lung and extranodal marginal zone/low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is reported. Primary pulmonary non-Hodgkin's lymphoma is relatively rare, however, the majority of these lesions are low-grade B-cell lymphomas of MALT. After the stomach, the lung is the second most common location for such latter lesions. Lung adenocarcinoma in selected countries is fast becoming the leading form of non small-cell lung carcinoma. To our knowledge, this synchronous occurrence in the lung has not been previously reported. Such associations have been primarily limited to gastric lesions where an association with Helicobacter pylori infection has been identified. This case report highlights the importance of adjunctive diagnostic investigations such as molecular techniques in conclusive analysis of synchronous cases such as ours.

The immunohistochemical expression of bcl-2 and p53 proteins was evaluated in formalin-fixed, paraffin-embedded surgical specimens from 212 patients with primary gastric lymphoma. bcl-2 protein was found to be expressed in 145 specimens (68%). Among the 179 specimens with B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), bcl-2 positivity decreased significantly as the histological grade advanced; bcl-2 was expressed in 93% of low-grade tumors, 88% of mixed-grade (low-grade with a focal high-grade component) tumors, and 44% of high-grade tumors (Cochran's linear trend test; P<.001). p53 protein expression was detected in 43 of 212 cases (20%). Among the B-cell MALT lymphomas, p53 positivity increased significantly as the histological grade advanced; p53 was expressed in 6% of low-grade tumors, 12% of mixed-grade tumors, and 31% of high-grade tumors (Cochran's linear trend test; P<.001). An inverse correlation was observed between the expression of bcl-2 and p53 in all 212 lymphomas (gamma = -0.531; P<.05) as well as in all 179 B-cell MALT lymphomas (gamma = -0.671; P<.01). Although the bcl-2 expression did not correlate with the patient survival, the p53 positive cases showed a significantly poorer prognosis compared with the p53 negative cases (log-rank test; P<.05). These results suggest that the expression of bcl-2 and p53 may, therefore, be associated with the transition from low-grade to high-grade tumors in primary gastric lymphoma.