MALT1 gene rearrangements and NF-kappaB activation involving p65 and p50 are absent or rare in primary MALT lymphomas of the breast.
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.
Talwalkar
Sameer S
SS
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Valbuena
Jose R
JR
Abruzzo
Lynne V
LV
Admirand
Joan H
JH
Konoplev
Sergej N
SN
Bueso-Ramos
Carlos E
CE
Medeiros
L Jeffrey
LJ
D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074018:B-Cell CLL-Lymphoma 10 Protein; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D018567:Breast Neoplasms, Male / Q000235:genetics; D020169:Caspases / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D018442:Lymphoma, B-Cell, Marginal Zone / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics; D008297:Male; D008875:Middle Aged; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D016328:NF-kappa B / Q000032:analysis*; D052002:NF-kappa B p50 Subunit / Q000032:analysis; D009363:Neoplasm Proteins / Q000235:genetics*; D051996:Transcription Factor RelA / Q000032:analysis
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009363:Neoplasm Proteins; D051996:Transcription Factor RelA; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein