MALT1 gene rearrangements and NF-kappaB activation involving p65 and p50 are absent or rare in primary MALT lymphomas of the breast

• Published in: Modern pathology 2006-11, Vol.19 (11), p.1402-1408
• Main Authors: Talwalkar, Sameer S, Valbuena, Jose R, Abruzzo, Lynne V, Admirand, Joan H, Konoplev, Sergej N, Bueso-Ramos, Carlos E, Medeiros, L Jeffrey
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - analysis; Adult; Aged; Aged, 80 and over; B-Cell CLL-Lymphoma 10 Protein; Breast Neoplasms - chemistry; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Breast Neoplasms, Male - genetics; Caspases - genetics; Female; Gene Expression Regulation, Neoplastic; Gene Rearrangement; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Lymphoma, B-Cell, Marginal Zone - chemistry; Lymphoma, B-Cell, Marginal Zone - genetics; Lymphoma, B-Cell, Marginal Zone - pathology; Lymphoma, Large B-Cell, Diffuse - genetics; Male; Middle Aged; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; Neoplasm Proteins - genetics; NF-kappa B - analysis; NF-kappa B p50 Subunit - analysis; Transcription Factor RelA - analysis
• ISSN: 0893-3952

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-kappaB 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-kappaB 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-kappaB p65 (n=8) and p50 (n=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-kappaB p65 (n=11) showed cytoplasmic staining in all cases, whereas p50 (n=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-kappaB 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-kappaB p50 activation in a subset differs from breast MALT lymphomas.