No abstract

Lymphomas involving the breast account for approximately 2% of extranodal and <1% of all non-Hodgkin lymphomas. Our aim in this study was to classify breast lymphomas using the World Health Organization classification and then compare this classification with clinical, histologic, and radiologic findings as well as survival. The study group included 106 patients with breast lymphoma (105 women and 1 man). The neoplasms were divided into 2 groups based on extent of disease at initial diagnosis: localized disease (n=50) and disseminated disease (n=56). The follow-up period ranged from 4 to 252 months (median, 49 mo). Almost all (97%) patients presented with a palpable breast mass or masses. In the localized group, diffuse large B-cell lymphoma (DLBCL) was most frequent (n=32, 64%). In the disseminated group, follicular lymphoma was most frequent and exclusive to this group (P=0.0004). Mucosa-associated lymphoid tissue lymphomas occurred in both groups without a significant difference in frequency. A variety of other types of B-cell and T-cell non-Hodgkin lymphomas and classical Hodgkin lymphoma involved the breast at much lower frequency; most of these neoplasms involved the breast as part of disseminated disease. The clinical presentation correlated with radiologic findings: localized lymphomas presented as solitary masses, whereas disseminated lymphomas commonly presented as multifocal masses. There was a significant difference in the disease-free survival between patients with localized and disseminated DLBCL (P=0.003). In the disseminated group, patients with DLBCL had a worse disease-free survival compared with patients with mucosa-associated lymphoid tissue lymphoma or follicular lymphoma (P=0.01).

To develop a model incorporating relevant prognostic biomarkers for untreated chronic lymphocytic leukemia patients, we re-analyzed the raw data from four published gene expression profiling studies. We selected 88 candidate biomarkers linked to immunoglobulin heavy-chain variable region gene (IgV H ) mutation status and produced a reliable and reproducible microfluidics quantitative real-time polymerase chain reaction array. We applied this array to a training set of 29 purified samples from previously untreated patients. In an unsupervised analysis, the samples clustered into two groups. Using a cutoff point of 2% homology to the germline IgV H sequence, one group contained all 14 IgV H -unmutated samples; the other contained all 15 mutated samples. We confirmed the differential expression of 37 of the candidate biomarkers using two-sample t-tests. Next, we constructed 16 different models to predict IgV H mutation status and evaluated their performance on an independent test set of 20 new samples. Nine models correctly classified 11 of 11 IgV H -mutated cases and eight of nine IgV H -unmutated cases, with some models using three to seven genes. Thus, we can classify cases with 95% accuracy based on the expression of as few as three genes. (J Mol Diagn 2007, 9:456 -555;

Mucosa associated lymphoid tissue (MALT) lymphomas arising in the breast are uncommon and few cases have been assessed for MALT lymphoma-associated translocations, BCL-10 expression, or NF-jB activation. In this study, we analyzed eight cases of primary breast MALT lymphoma. We also included 14 cases of primary breast diffuse large B-cell lymphoma since some of these may represent transformation of MALT lymphoma, known to occur at extra-mammary MALT sites. All cases were assessed for MALT1 gene rearrangements by fluorescence in situ hybridization (FISH). Using immunohistochemical methods, all cases were assessed for BCL-10, and subsets were assessed for NF-jB p65 and p50. None of the cases had MALT1 gene rearrangements by FISH. Of eight MALT lymphomas, BCL-10 was positive in seven (88%), with moderate nuclear and cytoplasmic staining in six, and a weak cytoplasmic staining in one. NF-jB p65 (n ¼ 8) and p50 (n ¼ 5) were negative or showed only cytoplasmic staining (ie inactivated) in all cases. Of 14 diffuse large B-cell lymphoma cases, BCL-10 was positive in 12 (87%), with weak-to-moderate cytoplasmic staining in 10, weak cytoplasmic and focally nuclear staining in one, and a moderate-to-strong nuclear and cytoplasmic staining in one. NF-jB p65 (n ¼ 11) showed cytoplasmic staining in all cases, whereas p50 (n ¼ 8) showed nuclear positivity (ie activated) in two (25%) cases. We conclude that MALT1 gene rearrangements are absent or rare in primary breast MALT lymphoma and diffuse large B-cell lymphoma. In MALT lymphomas, the moderate BCL-10 nuclear expression in six neoplasms is inconsistent with the FISH results, suggesting that BCL-10 immunostaining overestimates the frequency of MALT1 gene rearrangements. We also could not demonstrate NF-jB activation using nuclear staining for p65 and p50. In contrast, breast diffuse large B-cell lymphomas are heterogeneous. Weak cytoplasmic BCL-10 staining in most cases and evidence of NF-jB p50 activation in a subset differs from breast MALT lymphomas.