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Increased expression of cyclin D1 is notoriously associated with mantle cell lymphoma because of translocation t(11;14)(q13;q32) or variants involving the cyclin D1 gene. We present an unusual case of CD5-negative diffuse large B-cell lymphoma expressing cyclin D1 in the absence of translocation by fluorescence in situ hybridization analysis. Using array-comparative genomic hybridization, we found a complex karyotype without the characteristic chromosomal aberrations accompanying cyclin D1 translocation in mantle cell lymphoma; instead, there was monoallelic deletion of AKT interacting protein and glycogen synthase kinase-3 β genes, both involved in the AKT/glycogen synthase kinase-3 β cascade-controlling nuclear levels of cyclin D1. These findings suggest that posttranslational events regulating cyclin D1 activity may take place also in a subset of diffuse large B-cell lymphomas and contribute to lymphomagenesis. As a consequence, the sole cyclin D1 positivity by immunohistochemistry may not be enough to distinguish pleomorphic/blastoid mantle cell lymphoma from diffuse large B-cell lymphoma. Search for t(11;14) with fluorescence in situ hybridization probes should always be performed in doubtful cases., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Splenic marginal zone B-cell lymphoma is characterized by high genetic heterogeneity, and hepatitis C virus infection seems to be involved in a subset of patients. The aims of the analysis were to identify potential genetic alterations related to hepatitis C virus status, IgV(H) gene mutational status, and prognostic categories identified in a multicenter study (Blood 2006;107:4643). Genome-wide array comparative genomic hybridization at a 100-kilobase (kb) resolution was performed in 34 patients with splenic marginal zone B-cell lymphoma, 12 of whom were hepatitis C virus positive. Array-comparative genomic hybridization experiments revealed no copy number alterations in 10 patients (4 were hepatitis C virus positive). A median of 5.6 and 3.8 copy number alterations were detected in hepatitis C virus-positive and in hepatitis C virus-negative patients, respectively. The most frequent copy number alterations involved chromosomes 7 and 17 (21% and 24%, respectively). Except for Xp gain (P = .01), no differences in common alterations were found between hepatitis C virus-positive and hepatitis C virus-negative cases. Unmutated status of the IgV(H) gene was related to del(7q) (P = .04) and dup(12q) (P = .03). The high-risk group identified according to the new splenic marginal zone B-cell lymphoma prognostic score was associated with del(7q) (P = .01) and del(17p) (P = .02). Hepatitis C virus-positive splenic marginal zone B-cell lymphoma patients have no specific chromosome alterations. Patients with poor prognosis are characterized by distinctive imbalances.

This study analyzes the pathologic and molecular features of 5 cases of primary cutaneous large B-cell lymphoma of the leg (PCLBCL-leg), recently included in the European Organization for Research and Treatment of Cancer (EORTC) classification of primary cutaneous lymphoma. PCLBCL-leg accounts for 5% to 10% of all primary cutaneous B-cell lymphoma (PCBCL), usually affects elderly patients and carries a worse prognosis than other forms of PCBCL. It has been proposed that the malignant cells of PCLBCL-leg originate from germinal center (GC)-related cells, but their effective normal counterpart is unclear, and the rationale behind the inclusion of this lymphoma as a separate entity is based on its prognosis rather than on its proved histogenesis. All of our cases of PCLBCL-leg morphologically resembled diffuse large B-cell lymphoma (DLBCL), but to better define their histogenesis, we also analyzed various phenotypic and genotypic markers, including mutations of the Ig and of BCL-6 genes, as well as expression of the bcl-6, MUM1, and CD138/syndecan-1 proteins. Immunohistochemically, all of our cases stained for the L-26/CD20cy and CD79a antigens and expressed the bcl-2, bcl-6, and MUM-1 proteins but were negative for both the CD10/CALLA and CD138 antigens. With respect to molecular analysis, the lymphoma population of all PCLBCL-leg carried hypermutation of Ig genes, and all but 1 case also harbored mutations of the BCL-6 gene. Our results indicate that PCLBCL-leg are similar both under the morphofunctional and molecular profiles to most DLBCL of other sites. Thus, caution seems justified before definitely considering PCLBCL of the leg as a distinct entity., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

The spectrum of CD30+ cutaneous lymphoproliferative disorders is characterized by the histology of a high-grade lymphoma but frequent clinical regression of skin lesions in lymphomatoid papulosis (LyP) and occasional regression in CD30+ large cell lymphomas (LCLs). A recent study shows that apoptosis may be a significant mechanism of regression of LyP (Arch Dermatol 133:828-833, 1997). Therefore, we studied expression of proteins that induce apoptosis, including CD27, CD40, CD95, and nerve growth factor receptor (NGF-R), as well as anti-apoptotic protein bcl-2 in skin lesions from 25 patients within the spectrum of CD30+ cutaneous lymphoma. Our results show consistent expression of CD95 (APO-1/Fas), but rare or absent expression of CD27, CD40, and NGF-R on tumor cells from both regressing LyP lesions and nonregressing CD30+ lymphomas. Bcl-2 was expressed at low levels in LyP and at high levels in pleomorphic CD30+ lymphomas. These results indicate that, in addition to CD30, CD95 expression is preferentially expressed at high levels in all cutaneous CD30+ lymphomas and suggest that CD95 may play a role in the regression of CD30+ skin lesions. Expression of bcl-2 appears to protect tumor cells from apoptosis in CD30+ lymphoproliferative disorders.

Splenic marginal zone (MRZ) cell lymphoma is a recently described neoplasm arising in a unique compartment of splenic white pulp, producing massive splenomegaly and spreading to bone marrow and distant lymph nodes. We report three cases of splenic lymphoma that morphologically and immunohistochemically appear to originate from MRZ cells that presented as indolent neoplasms involving the spleen but with no or only moderate enlargement of the organ, presumably representing an early clinical stage of this disorder. Despite the evidence of involvement of the liver in one case, lymph nodes and bone marrow proved to be uninvolved. Histologically, the three spleens showed similar features, being characterized by the involvement of white pulp follicles and periarteriolar lymphoid sheaths by medium-sized lymphoid cells with slightly irregular nuclei and ample cytoplasm. Immunohistochemically, all the specimens expressed a series of B-lineage markers that, in contrast to specimens of monocytoid B cell lymphoma (MBCL) and hairy cell leukemia (HCL) studied for comparison, did not react with KiB3, LN1, and DBA.44 monoclonal antibodies.